GSEA Class2: Canonical Pathways enriched in each subtypes of mRNAseq_cNMF in PRAD-TP

Prostate Adenocarcinoma (Primary solid tumor)

02 April 2015 | analyses__2015_04_02

Maintainer Information

Citation Information

Maintained by Juok Cho (Broad Institute)

Cite as Broad Institute TCGA Genome Data Analysis Center (2015): GSEA Class2: Canonical Pathways enriched in each subtypes of mRNAseq_cNMF in PRAD-TP. Broad Institute of MIT and Harvard. doi:10.7908/C1ZW1K1K

Overview

Introduction

This pipeline performs Gene Set Enrichment Analysis (GSEA) using The Broad Institute GSEA tool with MSigDB - Class2: Canonical Pathways gene sets. For a given phenotype subtype, it shows what pathways are significantly enriched in each subtype by comparing gene expression profiles between subtypes. Here, the phenotype is mRNAseq_cNMF subtypes in PRAD-TP. This pipeline has the following features:

For each subtype, calculates enrichment scores (ES) using signal to noise (S2N) that checks similarity between subtypes in expression level then calculates p values through permutation test.
Lists pathways significantly enriched in each phenotype subtype and their enrichment scores (ES).
Lists top 20 core genes enriched in each significant gene set and their enrichment scores (ES).
Checks if the top core genes are up-regulated or down-regulated.
Checks if the top core genes are high expressed or low expressed.
Checks if the top core genes are significantly differently expressed genes.

Summary

Table 1. Get Full Table basic data info

basic data info
Number of Gene Sets: 193
Number of samples: 497
Original number of Gene Sets: 404
Maximum gene set size: 388

Table 2. Get Full Table pheno data info

phenotype info
pheno.type: 1 - 3 :[ clus1 ] 147
pheno.type: 2 - 3 :[ clus2 ] 175
pheno.type: 3 - 3 :[ clus3 ] 175

For the expression subtypes of 18274 genes in 498 samples, GSEA found enriched gene sets in each cluster using 497 gene sets in MSigDB canonical pathways. Top enriched gene sets are listed as below.

clus1

Top enriched gene sets are BIOCARTA AGR PATHWAY, BIOCARTA BCR PATHWAY, BIOCARTA BIOPEPTIDES PATHWAY, BIOCARTA HDAC PATHWAY, BIOCARTA EGF PATHWAY, BIOCARTA FCER1 PATHWAY, BIOCARTA FMLP PATHWAY, BIOCARTA GH PATHWAY, BIOCARTA HIVNEF PATHWAY, BIOCARTA IL2RB PATHWAY

And common core enriched genes are PLCG2, ATP6V0A4, ATP6V0D2, ATP6V1B1, ATP6V1G3, CXCR1, CXCR2, EGFR, MET, NTRK1

clus2

Top enriched gene sets are KEGG GLYCOLYSIS GLUCONEOGENESIS, KEGG FRUCTOSE AND MANNOSE METABOLISM, KEGG FATTY ACID METABOLISM, KEGG OXIDATIVE PHOSPHORYLATION, KEGG PYRIMIDINE METABOLISM, KEGG GLYCINE SERINE AND THREONINE METABOLISM, KEGG VALINE LEUCINE AND ISOLEUCINE DEGRADATION, KEGG TYROSINE METABOLISM, KEGG GLUTATHIONE METABOLISM, KEGG AMINO SUGAR AND NUCLEOTIDE SUGAR METABOLISM

And common core enriched genes are ACAT2, ALDH2, ALDH3A2, ALDH7A1, ECHS1, ABAT, ACAA1, ACAA2, ACADSB, EHHADH

clus3

Top enriched gene sets are BIOCARTA CARM ER PATHWAY, BIOCARTA HIVNEF PATHWAY, BIOCARTA MPR PATHWAY, BIOCARTA TNFR1 PATHWAY, KEGG CITRATE CYCLE TCA CYCLE, KEGG PENTOSE PHOSPHATE PATHWAY, KEGG N GLYCAN BIOSYNTHESIS, KEGG AMINOACYL TRNA BIOSYNTHESIS, KEGG RIBOSOME, KEGG RNA DEGRADATION

And common core enriched genes are CARS2, DARS, DARS2, EARS2, EPRS, FARSB, GARS, IARS, IARS2, LARS

Results

Subtype clus1 enriched pathways

Table 3. Get Full Table This table shows top 10 pathways which are significantly enriched in cluster clus1. It displays only significant gene sets satisfying nom.p.val.threshold (-1), fwer.p.val.threshold (-1) , fdr.q.val.threshold (0.25) and the default table is sorted by Normalized Enrichment Score (NES). Further details on NES statistics, please visit The Broad GSEA website.

GeneSet(GS)	Size(#genes)	genes.ES.table	ES	NES	NOM.p.val	FDR.q.val	FWER.p.val	Tag..	Gene..	Signal	FDR..median.	glob.p.val
BIOCARTA AGR PATHWAY	35	genes.ES.table	0.61	1.5	0.048	0.22	0.85	0.4	0.22	0.31	0.15	0.015
BIOCARTA BCR PATHWAY	33	genes.ES.table	0.54	1.4	0.088	0.17	0.92	0.33	0.23	0.26	0.13	0.001
BIOCARTA BIOPEPTIDES PATHWAY	39	genes.ES.table	0.4	1.3	0.17	0.23	0.99	0.31	0.26	0.23	0.19	0
BIOCARTA HDAC PATHWAY	26	genes.ES.table	0.44	1.3	0.17	0.21	0.98	0.62	0.4	0.37	0.17	0
BIOCARTA EGF PATHWAY	30	genes.ES.table	0.51	1.4	0.085	0.18	0.94	0.53	0.36	0.34	0.14	0.002
BIOCARTA FCER1 PATHWAY	37	genes.ES.table	0.56	1.5	0.075	0.18	0.9	0.3	0.2	0.24	0.13	0.003
BIOCARTA FMLP PATHWAY	34	genes.ES.table	0.46	1.5	0.082	0.18	0.9	0.41	0.36	0.26	0.13	0.003
BIOCARTA GH PATHWAY	26	genes.ES.table	0.54	1.5	0.07	0.17	0.9	0.5	0.32	0.34	0.13	0.002
BIOCARTA HIVNEF PATHWAY	57	genes.ES.table	0.35	1.4	0.14	0.19	0.95	0.37	0.4	0.22	0.15	0.004
BIOCARTA IL2RB PATHWAY	37	genes.ES.table	0.58	1.5	0.073	0.17	0.91	0.43	0.21	0.34	0.13	0.001

genes ES table in pathway: BIOCARTA AGR PATHWAY

Table S1. Get Full Table This table shows a Running Enrichment Score (RES) of each gene in this pathway, that is, the enrichment score at this point in the ranked list of genes. All genes are ranked by Signal-to-Noise (S2N), a measure of similarity as default and are used to obtain ES matrix of all genes. In this way, GSEA tool uses expression pattern of not only overlapped genes but also not-overlapped genes to produce ES matrix.

Rank	GENE	SYMBOL	DESC	LIST.LOC	S2N	RES	CORE_ENRICHMENT
1	CXCR2	CXCR2	CXCR2	59	0.74	0.09	YES
2	ATP6V0A4	ATP6V0A4	ATP6V0A4	187	0.6	0.16	YES
3	PTPRZ1	PTPRZ1	PTPRZ1	247	0.57	0.23	YES
4	CXCL1	CXCL1	CXCL1	304	0.54	0.29	YES
5	ATP6V1G3	ATP6V1G3	ATP6V1G3	342	0.52	0.36	YES
6	ATP6V0D2	ATP6V0D2	ATP6V0D2	469	0.48	0.41	YES
7	MET	MET	MET	692	0.42	0.45	YES
8	IL8	IL8	IL8	1858	0.27	0.42	YES
9	PLCG2	PLCG2	PLCG2	2063	0.25	0.44	YES
10	CCL5	CCL5	CCL5	2197	0.24	0.46	YES
11	ATP6V1B1	ATP6V1B1	ATP6V1B1	2221	0.24	0.49	YES
12	EGFR	EGFR	EGFR	2751	0.2	0.49	YES
13	MAP3K14	MAP3K14	MAP3K14	2881	0.2	0.51	YES
14	JAM2	JAM2	JAM2	2913	0.19	0.53	YES
15	CXCR1	CXCR1	CXCR1	3005	0.19	0.55	YES
16	HBEGF	HBEGF	HBEGF	3103	0.18	0.56	YES
17	JAM3	JAM3	JAM3	3421	0.17	0.57	YES
18	PAK1	PAK1	PAK1	4017	0.14	0.55	NO
19	TCIRG1	TCIRG1	TCIRG1	4604	0.11	0.54	NO
20	NFKB1	NFKB1	NFKB1	5345	0.085	0.51	NO
21	F11R	F11R	F11R	5389	0.084	0.51	NO
22	JUN	JUN	JUN	5675	0.076	0.51	NO
23	NFKBIA	NFKBIA	NFKBIA	5963	0.068	0.5	NO
24	ATP6V1G2	ATP6V1G2	ATP6V1G2	6717	0.05	0.47	NO
25	ADAM17	ADAM17	ADAM17	6766	0.049	0.47	NO
26	ADAM10	ADAM10	ADAM10	6804	0.049	0.47	NO
27	NOD1	NOD1	NOD1	7336	0.039	0.45	NO
28	ATP6V1C2	ATP6V1C2	ATP6V1C2	7451	0.037	0.45	NO
29	SRC	SRC	SRC	7509	0.036	0.45	NO
30	IGSF5	IGSF5	IGSF5	7572	0.035	0.45	NO
31	IKBKB	IKBKB	IKBKB	7763	0.032	0.44	NO
32	MAPK10	MAPK10	MAPK10	7764	0.032	0.45	NO
33	MAPK14	MAPK14	MAPK14	7767	0.032	0.45	NO
34	MAPK13	MAPK13	MAPK13	7964	0.029	0.44	NO
35	ATP6V0A2	ATP6V0A2	ATP6V0A2	8133	0.027	0.44	NO
36	ATP6V0D1	ATP6V0D1	ATP6V0D1	8215	0.026	0.44	NO
37	MAPK8	MAPK8	MAPK8	8275	0.025	0.44	NO
38	PTPN11	PTPN11	PTPN11	8456	0.022	0.43	NO
39	LYN	LYN	LYN	8481	0.022	0.43	NO
40	ATP6V1B2	ATP6V1B2	ATP6V1B2	8965	0.016	0.41	NO
41	CHUK	CHUK	CHUK	9057	0.015	0.4	NO
42	MAP2K4	MAP2K4	MAP2K4	9215	0.013	0.4	NO
43	MAPK11	MAPK11	MAPK11	9273	0.012	0.4	NO
44	ATP6V0A1	ATP6V0A1	ATP6V0A1	9673	0.0077	0.37	NO
45	PLCG1	PLCG1	PLCG1	9689	0.0076	0.37	NO
46	RELA	RELA	RELA	9970	0.0046	0.36	NO
47	IKBKG	IKBKG	IKBKG	9995	0.0042	0.36	NO
48	CDC42	CDC42	CDC42	10545	-0.0019	0.33	NO
49	CASP3	CASP3	CASP3	11537	-0.012	0.28	NO
50	ATP6V1H	ATP6V1H	ATP6V1H	11558	-0.012	0.28	NO
51	ATP6V1D	ATP6V1D	ATP6V1D	11582	-0.012	0.28	NO
52	ATP6V1E1	ATP6V1E1	ATP6V1E1	11879	-0.015	0.26	NO
53	RAC1	RAC1	RAC1	11885	-0.015	0.26	NO
54	CSK	CSK	CSK	12373	-0.02	0.24	NO
55	GIT1	GIT1	GIT1	12558	-0.022	0.23	NO
56	TJP1	TJP1	TJP1	13135	-0.029	0.2	NO
57	ATP6AP1	ATP6AP1	ATP6AP1	13384	-0.031	0.2	NO
58	ATP6V1A	ATP6V1A	ATP6V1A	13453	-0.032	0.2	NO
59	ATP6V1C1	ATP6V1C1	ATP6V1C1	13508	-0.033	0.2	NO
60	ATP6V0C	ATP6V0C	ATP6V0C	14278	-0.042	0.16	NO
61	ATP6V1E2	ATP6V1E2	ATP6V1E2	14448	-0.044	0.16	NO
62	MAPK9	MAPK9	MAPK9	14539	-0.045	0.16	NO
63	ATP6V0B	ATP6V0B	ATP6V0B	15198	-0.056	0.13	NO
64	ATP6V1F	ATP6V1F	ATP6V1F	15288	-0.058	0.13	NO
65	ATP6V1G1	ATP6V1G1	ATP6V1G1	15661	-0.064	0.12	NO
66	ATP6V0E2	ATP6V0E2	ATP6V0E2	16306	-0.082	0.092	NO
67	MAPK12	MAPK12	MAPK12	17086	-0.12	0.064	NO

Figure S1. Get High-res Image This plot shows mRNAseq_cNMF expression data heatmap (on the left) a RunningEnrichmentScore(RES) plot (on the top right) and a Signal2Noise(S2N) plot (on the bottom right) of genes in the pathway: BIOCARTA AGR PATHWAY.

Figure S2. Get High-res Image For the top 5 core enriched genes in the pathway: BIOCARTA AGR PATHWAY, this volcano plot shows how much they are up/down-regulated and significant. The significance was calculated by empirical bayesian fit

genes ES table in pathway: BIOCARTA BCR PATHWAY

Table S2. Get Full Table This table shows a Running Enrichment Score (RES) of each gene in this pathway, that is, the enrichment score at this point in the ranked list of genes. All genes are ranked by Signal-to-Noise (S2N), a measure of similarity as default and are used to obtain ES matrix of all genes. In this way, GSEA tool uses expression pattern of not only overlapped genes but also not-overlapped genes to produce ES matrix.

Rank	GENE	SYMBOL	DESC	LIST.LOC	S2N	RES	CORE_ENRICHMENT
1	NTF4	NTF4	NTF4	33	0.79	0.063	YES
2	CALML3	CALML3	CALML3	79	0.71	0.12	YES
3	TP73	TP73	TP73	192	0.6	0.16	YES
4	NTRK3	NTRK3	NTRK3	207	0.6	0.21	YES
5	NTF3	NTF3	NTF3	432	0.49	0.24	YES
6	BDNF	BDNF	BDNF	548	0.46	0.27	YES
7	NGFR	NGFR	NGFR	710	0.42	0.29	YES
8	NTRK2	NTRK2	NTRK2	844	0.39	0.32	YES
9	NTRK1	NTRK1	NTRK1	1124	0.35	0.33	YES
10	PIK3CD	PIK3CD	PIK3CD	1291	0.32	0.35	YES
11	BCL2	BCL2	BCL2	1377	0.32	0.37	YES
12	IRAK3	IRAK3	IRAK3	1539	0.3	0.38	YES
13	FASLG	FASLG	FASLG	1579	0.3	0.4	YES
14	PIK3CG	PIK3CG	PIK3CG	1880	0.26	0.41	YES
15	SHC3	SHC3	SHC3	2004	0.26	0.42	YES
16	IRS1	IRS1	IRS1	2052	0.25	0.44	YES
17	PLCG2	PLCG2	PLCG2	2063	0.25	0.46	YES
18	IRAK2	IRAK2	IRAK2	2211	0.24	0.47	YES
19	CAMK4	CAMK4	CAMK4	2283	0.23	0.49	YES
20	IRS4	IRS4	IRS4	3532	0.16	0.43	NO
21	PIK3R1	PIK3R1	PIK3R1	3640	0.16	0.44	NO
22	CAMK2A	CAMK2A	CAMK2A	3918	0.14	0.43	NO
23	MAP3K1	MAP3K1	MAP3K1	4267	0.13	0.42	NO
24	TRAF6	TRAF6	TRAF6	4412	0.12	0.43	NO
25	CAMK2G	CAMK2G	CAMK2G	4507	0.12	0.43	NO
26	SH2B3	SH2B3	SH2B3	4574	0.11	0.44	NO
27	PIK3R5	PIK3R5	PIK3R5	4684	0.11	0.44	NO
28	RPS6KA5	RPS6KA5	RPS6KA5	5110	0.093	0.42	NO
29	NFKB1	NFKB1	NFKB1	5345	0.085	0.42	NO
30	MAPK7	MAPK7	MAPK7	5666	0.076	0.41	NO
31	JUN	JUN	JUN	5675	0.076	0.41	NO
32	MAP3K3	MAP3K3	MAP3K3	5778	0.074	0.41	NO
33	CALM1	CALM1	CALM1	5943	0.069	0.41	NO
34	NFKBIA	NFKBIA	NFKBIA	5963	0.068	0.41	NO
35	GAB1	GAB1	GAB1	6086	0.065	0.41	NO
36	MAP3K5	MAP3K5	MAP3K5	6308	0.06	0.4	NO
37	PIK3CA	PIK3CA	PIK3CA	6344	0.059	0.41	NO
38	SHC4	SHC4	SHC4	6407	0.057	0.41	NO
39	CALML6	CALML6	CALML6	6430	0.057	0.41	NO
40	NFKBIE	NFKBIE	NFKBIE	6532	0.054	0.41	NO
41	SOS1	SOS1	SOS1	6586	0.053	0.41	NO
42	NGF	NGF	NGF	6666	0.052	0.41	NO
43	SOS2	SOS2	SOS2	6925	0.046	0.4	NO
44	IRAK4	IRAK4	IRAK4	6938	0.046	0.4	NO
45	RAPGEF1	RAPGEF1	RAPGEF1	7004	0.045	0.4	NO
46	CRKL	CRKL	CRKL	7381	0.038	0.39	NO
47	MAPK3	MAPK3	MAPK3	7510	0.036	0.38	NO
48	CRK	CRK	CRK	7526	0.036	0.38	NO
49	RAP1B	RAP1B	RAP1B	7621	0.034	0.38	NO
50	PRDM4	PRDM4	PRDM4	7665	0.034	0.38	NO
51	IKBKB	IKBKB	IKBKB	7763	0.032	0.38	NO
52	MAPK10	MAPK10	MAPK10	7764	0.032	0.38	NO
53	MAPK14	MAPK14	MAPK14	7767	0.032	0.39	NO
54	RPS6KA2	RPS6KA2	RPS6KA2	7778	0.032	0.39	NO
55	FOXO3	FOXO3	FOXO3	7792	0.032	0.39	NO
56	ARHGDIB	ARHGDIB	ARHGDIB	7853	0.031	0.39	NO
57	RAP1A	RAP1A	RAP1A	7914	0.03	0.39	NO
58	YWHAH	YWHAH	YWHAH	7929	0.029	0.39	NO
59	KIDINS220	KIDINS220	KIDINS220	7946	0.029	0.39	NO
60	MAPK13	MAPK13	MAPK13	7964	0.029	0.39	NO
61	CAMK2D	CAMK2D	CAMK2D	7978	0.029	0.39	NO
62	SORT1	SORT1	SORT1	8022	0.028	0.39	NO
63	IRS2	IRS2	IRS2	8181	0.026	0.39	NO
64	CALML5	CALML5	CALML5	8266	0.025	0.38	NO
65	MAPK8	MAPK8	MAPK8	8275	0.025	0.39	NO
66	TP53	TP53	TP53	8348	0.024	0.38	NO
67	MAPKAPK2	MAPKAPK2	MAPKAPK2	8420	0.023	0.38	NO
68	PTPN11	PTPN11	PTPN11	8456	0.022	0.38	NO
69	SHC1	SHC1	SHC1	8477	0.022	0.38	NO
70	AKT3	AKT3	AKT3	8806	0.018	0.37	NO
71	PSEN1	PSEN1	PSEN1	8989	0.016	0.36	NO
72	FRS2	FRS2	FRS2	9049	0.015	0.36	NO
73	MAPK1	MAPK1	MAPK1	9197	0.013	0.35	NO
74	MAPK11	MAPK11	MAPK11	9273	0.012	0.34	NO
75	ZNF274	ZNF274	ZNF274	9368	0.012	0.34	NO
76	ABL1	ABL1	ABL1	9540	0.0094	0.33	NO
77	PLCG1	PLCG1	PLCG1	9689	0.0076	0.32	NO
78	MAP2K7	MAP2K7	MAP2K7	9779	0.0066	0.32	NO
79	MAP2K5	MAP2K5	MAP2K5	9847	0.006	0.32	NO
80	RELA	RELA	RELA	9970	0.0046	0.31	NO
81	YWHAB	YWHAB	YWHAB	10027	0.0038	0.31	NO
82	RHOA	RHOA	RHOA	10131	0.0025	0.3	NO
83	SH2B1	SH2B1	SH2B1	10207	0.0017	0.3	NO
84	RPS6KA3	RPS6KA3	RPS6KA3	10256	0.0012	0.3	NO
85	CDC42	CDC42	CDC42	10545	-0.0019	0.28	NO
86	GRB2	GRB2	GRB2	10644	-0.0028	0.28	NO
87	CALM3	CALM3	CALM3	11009	-0.0063	0.26	NO
88	NRAS	NRAS	NRAS	11024	-0.0065	0.26	NO
89	RAF1	RAF1	RAF1	11040	-0.0066	0.26	NO
90	NGFRAP1	NGFRAP1	NGFRAP1	11061	-0.0068	0.26	NO
91	AKT2	AKT2	AKT2	11216	-0.0087	0.25	NO
92	KRAS	KRAS	KRAS	11547	-0.012	0.23	NO
93	NFKBIB	NFKBIB	NFKBIB	11684	-0.013	0.22	NO
94	RAC1	RAC1	RAC1	11885	-0.015	0.21	NO
95	PRKCD	PRKCD	PRKCD	12025	-0.017	0.21	NO
96	SHC2	SHC2	SHC2	12319	-0.02	0.19	NO
97	CALM2	CALM2	CALM2	12360	-0.02	0.19	NO
98	CSK	CSK	CSK	12373	-0.02	0.19	NO
99	RPS6KA1	RPS6KA1	RPS6KA1	12407	-0.021	0.19	NO
100	AKT1	AKT1	AKT1	12627	-0.023	0.18	NO
101	RPS6KA6	RPS6KA6	RPS6KA6	13034	-0.028	0.16	NO
102	MAP2K2	MAP2K2	MAP2K2	13165	-0.029	0.16	NO
103	PIK3R2	PIK3R2	PIK3R2	13482	-0.032	0.14	NO
104	YWHAE	YWHAE	YWHAE	13897	-0.037	0.12	NO
105	GSK3B	GSK3B	GSK3B	13902	-0.037	0.13	NO
106	YWHAQ	YWHAQ	YWHAQ	13922	-0.038	0.13	NO
107	ATF4	ATF4	ATF4	13971	-0.038	0.13	NO
108	PIK3R3	PIK3R3	PIK3R3	14025	-0.039	0.13	NO
109	YWHAZ	YWHAZ	YWHAZ	14058	-0.039	0.13	NO
110	PIK3CB	PIK3CB	PIK3CB	14073	-0.039	0.13	NO
111	MAP2K1	MAP2K1	MAP2K1	14380	-0.043	0.12	NO
112	MAPK9	MAPK9	MAPK9	14539	-0.045	0.11	NO
113	ARHGDIA	ARHGDIA	ARHGDIA	14559	-0.045	0.12	NO
114	IRAK1	IRAK1	IRAK1	14991	-0.052	0.097	NO
115	YWHAG	YWHAG	YWHAG	15077	-0.054	0.097	NO
116	MAGED1	MAGED1	MAGED1	15122	-0.054	0.099	NO
117	BAX	BAX	BAX	15244	-0.057	0.097	NO
118	BAD	BAD	BAD	15633	-0.064	0.08	NO
119	RPS6KA4	RPS6KA4	RPS6KA4	15973	-0.072	0.068	NO
120	BRAF	BRAF	BRAF	16009	-0.073	0.072	NO
121	PDK1	PDK1	PDK1	16259	-0.08	0.064	NO
122	MAPK12	MAPK12	MAPK12	17086	-0.12	0.029	NO
123	RIPK2	RIPK2	RIPK2	17111	-0.12	0.037	NO
124	SH2B2	SH2B2	SH2B2	17407	-0.15	0.033	NO
125	CAMK2B	CAMK2B	CAMK2B	17615	-0.17	0.035	NO

Figure S3. Get High-res Image This plot shows mRNAseq_cNMF expression data heatmap (on the left) a RunningEnrichmentScore(RES) plot (on the top right) and a Signal2Noise(S2N) plot (on the bottom right) of genes in the pathway: BIOCARTA BCR PATHWAY.

Figure S4. Get High-res Image For the top 5 core enriched genes in the pathway: BIOCARTA BCR PATHWAY, this volcano plot shows how much they are up/down-regulated and significant. The significance was calculated by empirical bayesian fit

genes ES table in pathway: BIOCARTA BIOPEPTIDES PATHWAY

Table S3. Get Full Table This table shows a Running Enrichment Score (RES) of each gene in this pathway, that is, the enrichment score at this point in the ranked list of genes. All genes are ranked by Signal-to-Noise (S2N), a measure of similarity as default and are used to obtain ES matrix of all genes. In this way, GSEA tool uses expression pattern of not only overlapped genes but also not-overlapped genes to produce ES matrix.

Rank	GENE	SYMBOL	DESC	LIST.LOC	S2N	RES	CORE_ENRICHMENT
1	TMLHE	TMLHE	TMLHE	216	0.59	0.22	YES
2	PIPOX	PIPOX	PIPOX	254	0.56	0.43	YES
3	BBOX1	BBOX1	BBOX1	2813	0.2	0.36	NO
4	ALDH2	ALDH2	ALDH2	3065	0.18	0.42	NO
5	ALDH3A2	ALDH3A2	ALDH3A2	4461	0.12	0.39	NO
6	WHSC1L1	WHSC1L1	WHSC1L1	6060	0.066	0.33	NO
7	SETDB2	SETDB2	SETDB2	6817	0.048	0.31	NO
8	ASH1L	ASH1L	ASH1L	6862	0.047	0.32	NO
9	ALDH1B1	ALDH1B1	ALDH1B1	7110	0.043	0.32	NO
10	AASS	AASS	AASS	7539	0.036	0.32	NO
11	PLOD2	PLOD2	PLOD2	7558	0.035	0.33	NO
12	AASDH	AASDH	AASDH	7841	0.031	0.32	NO
13	ALDH9A1	ALDH9A1	ALDH9A1	8744	0.019	0.28	NO
14	SETD2	SETD2	SETD2	8815	0.018	0.28	NO
15	NSD1	NSD1	NSD1	8819	0.018	0.29	NO
16	SETD1A	SETD1A	SETD1A	8852	0.018	0.3	NO
17	OGDHL	OGDHL	OGDHL	8929	0.016	0.3	NO
18	ACAT2	ACAT2	ACAT2	9100	0.014	0.3	NO
19	OGDH	OGDH	OGDH	9193	0.013	0.3	NO
20	SETD1B	SETD1B	SETD1B	9229	0.013	0.3	NO
21	ALDH7A1	ALDH7A1	ALDH7A1	9874	0.0056	0.26	NO
22	DLST	DLST	DLST	10208	0.0017	0.25	NO
23	EHMT2	EHMT2	EHMT2	10291	0.00078	0.24	NO
24	SETD8	SETD8	SETD8	10415	-0.00064	0.24	NO
25	SUV420H1	SUV420H1	SUV420H1	10535	-0.0018	0.23	NO
26	PLOD1	PLOD1	PLOD1	10546	-0.0019	0.23	NO
27	HADHA	HADHA	HADHA	10587	-0.0023	0.23	NO
28	SETD7	SETD7	SETD7	10652	-0.0029	0.23	NO
29	EHMT1	EHMT1	EHMT1	10766	-0.0041	0.22	NO
30	AASDHPPT	AASDHPPT	AASDHPPT	10805	-0.0045	0.22	NO
31	SETDB1	SETDB1	SETDB1	11532	-0.012	0.19	NO
32	SETMAR	SETMAR	SETMAR	12408	-0.021	0.15	NO
33	DOT1L	DOT1L	DOT1L	12469	-0.021	0.15	NO
34	SUV39H2	SUV39H2	SUV39H2	12704	-0.024	0.15	NO
35	SUV39H1	SUV39H1	SUV39H1	12786	-0.025	0.15	NO
36	HADH	HADH	HADH	12902	-0.026	0.16	NO
37	AADAT	AADAT	AADAT	13035	-0.028	0.16	NO
38	GCDH	GCDH	GCDH	13654	-0.034	0.14	NO
39	PLOD3	PLOD3	PLOD3	14164	-0.04	0.13	NO
40	SUV420H2	SUV420H2	SUV420H2	15136	-0.055	0.095	NO
41	ECHS1	ECHS1	ECHS1	15444	-0.06	0.1	NO
42	ACAT1	ACAT1	ACAT1	15814	-0.068	0.11	NO
43	WHSC1	WHSC1	WHSC1	15819	-0.068	0.13	NO

Figure S5. Get High-res Image This plot shows mRNAseq_cNMF expression data heatmap (on the left) a RunningEnrichmentScore(RES) plot (on the top right) and a Signal2Noise(S2N) plot (on the bottom right) of genes in the pathway: BIOCARTA BIOPEPTIDES PATHWAY.

Figure S6. Get High-res Image For the top 5 core enriched genes in the pathway: BIOCARTA BIOPEPTIDES PATHWAY, this volcano plot shows how much they are up/down-regulated and significant. The significance was calculated by empirical bayesian fit

genes ES table in pathway: BIOCARTA HDAC PATHWAY

Table S4. Get Full Table This table shows a Running Enrichment Score (RES) of each gene in this pathway, that is, the enrichment score at this point in the ranked list of genes. All genes are ranked by Signal-to-Noise (S2N), a measure of similarity as default and are used to obtain ES matrix of all genes. In this way, GSEA tool uses expression pattern of not only overlapped genes but also not-overlapped genes to produce ES matrix.

Rank	GENE	SYMBOL	DESC	LIST.LOC	S2N	RES	CORE_ENRICHMENT
1	CFTR	CFTR	CFTR	65	0.72	0.14	YES
2	ATP6V0A4	ATP6V0A4	ATP6V0A4	187	0.6	0.25	YES
3	ATP6V1G3	ATP6V1G3	ATP6V1G3	342	0.52	0.34	YES
4	ATP6V0D2	ATP6V0D2	ATP6V0D2	469	0.48	0.42	YES
5	PRKCB	PRKCB	PRKCB	798	0.4	0.48	YES
6	PLCG2	PLCG2	PLCG2	2063	0.25	0.46	YES
7	ATP6V1B1	ATP6V1B1	ATP6V1B1	2221	0.24	0.5	YES
8	PRKCA	PRKCA	PRKCA	2960	0.19	0.5	NO
9	KCNQ1	KCNQ1	KCNQ1	4348	0.12	0.44	NO
10	TCIRG1	TCIRG1	TCIRG1	4604	0.11	0.45	NO
11	ADCY9	ADCY9	ADCY9	5104	0.093	0.44	NO
12	ERO1L	ERO1L	ERO1L	5901	0.07	0.41	NO
13	ATP6V1G2	ATP6V1G2	ATP6V1G2	6717	0.05	0.38	NO
14	KDELR3	KDELR3	KDELR3	7031	0.044	0.37	NO
15	ACTB	ACTB	ACTB	7269	0.04	0.36	NO
16	PRKCG	PRKCG	PRKCG	7414	0.038	0.36	NO
17	TJP2	TJP2	TJP2	7427	0.038	0.37	NO
18	ATP6V1C2	ATP6V1C2	ATP6V1C2	7451	0.037	0.38	NO
19	SLC12A2	SLC12A2	SLC12A2	8078	0.028	0.35	NO
20	ATP6V0A2	ATP6V0A2	ATP6V0A2	8133	0.027	0.35	NO
21	ATP6V0D1	ATP6V0D1	ATP6V0D1	8215	0.026	0.35	NO
22	PRKX	PRKX	PRKX	8754	0.019	0.32	NO
23	ATP6V1B2	ATP6V1B2	ATP6V1B2	8965	0.016	0.32	NO
24	MUC2	MUC2	MUC2	9444	0.01	0.29	NO
25	ATP6V0A1	ATP6V0A1	ATP6V0A1	9673	0.0077	0.28	NO
26	PLCG1	PLCG1	PLCG1	9689	0.0076	0.28	NO
27	PRKACA	PRKACA	PRKACA	9770	0.0066	0.28	NO
28	ATP6V0E1	ATP6V0E1	ATP6V0E1	11349	-0.01	0.19	NO
29	ATP6V1H	ATP6V1H	ATP6V1H	11558	-0.012	0.18	NO
30	ATP6V1D	ATP6V1D	ATP6V1D	11582	-0.012	0.18	NO
31	ATP6V1E1	ATP6V1E1	ATP6V1E1	11879	-0.015	0.17	NO
32	KDELR1	KDELR1	KDELR1	12279	-0.019	0.15	NO
33	SEC61A2	SEC61A2	SEC61A2	12573	-0.023	0.14	NO
34	PRKACB	PRKACB	PRKACB	13109	-0.029	0.12	NO
35	TJP1	TJP1	TJP1	13135	-0.029	0.12	NO
36	ACTG1	ACTG1	ACTG1	13191	-0.029	0.12	NO
37	ATP6AP1	ATP6AP1	ATP6AP1	13384	-0.031	0.12	NO
38	SEC61A1	SEC61A1	SEC61A1	13386	-0.031	0.13	NO
39	PDIA4	PDIA4	PDIA4	13450	-0.032	0.13	NO
40	ATP6V1A	ATP6V1A	ATP6V1A	13453	-0.032	0.14	NO
41	ATP6V1C1	ATP6V1C1	ATP6V1C1	13508	-0.033	0.14	NO
42	ARF1	ARF1	ARF1	13892	-0.037	0.12	NO
43	GNAS	GNAS	GNAS	13963	-0.038	0.13	NO
44	ATP6V0C	ATP6V0C	ATP6V0C	14278	-0.042	0.12	NO
45	ATP6V1E2	ATP6V1E2	ATP6V1E2	14448	-0.044	0.12	NO
46	KDELR2	KDELR2	KDELR2	14715	-0.048	0.11	NO
47	ATP6V0B	ATP6V0B	ATP6V0B	15198	-0.056	0.097	NO
48	ATP6V1F	ATP6V1F	ATP6V1F	15288	-0.058	0.1	NO
49	ATP6V1G1	ATP6V1G1	ATP6V1G1	15661	-0.064	0.095	NO
50	SEC61B	SEC61B	SEC61B	15787	-0.068	0.1	NO
51	ATP6V0E2	ATP6V0E2	ATP6V0E2	16306	-0.082	0.089	NO
52	SEC61G	SEC61G	SEC61G	16630	-0.095	0.089	NO

Figure S7. Get High-res Image This plot shows mRNAseq_cNMF expression data heatmap (on the left) a RunningEnrichmentScore(RES) plot (on the top right) and a Signal2Noise(S2N) plot (on the bottom right) of genes in the pathway: BIOCARTA HDAC PATHWAY.

Figure S8. Get High-res Image For the top 5 core enriched genes in the pathway: BIOCARTA HDAC PATHWAY, this volcano plot shows how much they are up/down-regulated and significant. The significance was calculated by empirical bayesian fit

genes ES table in pathway: BIOCARTA EGF PATHWAY

Table S5. Get Full Table This table shows a Running Enrichment Score (RES) of each gene in this pathway, that is, the enrichment score at this point in the ranked list of genes. All genes are ranked by Signal-to-Noise (S2N), a measure of similarity as default and are used to obtain ES matrix of all genes. In this way, GSEA tool uses expression pattern of not only overlapped genes but also not-overlapped genes to produce ES matrix.

Rank	GENE	SYMBOL	DESC	LIST.LOC	S2N	RES	CORE_ENRICHMENT
1	CXCR2	CXCR2	CXCR2	59	0.74	0.048	YES
2	FGFR2	FGFR2	FGFR2	284	0.55	0.073	YES
3	PSD2	PSD2	PSD2	471	0.48	0.096	YES
4	PIP5K1B	PIP5K1B	PIP5K1B	591	0.45	0.12	YES
5	SH3GL3	SH3GL3	SH3GL3	662	0.43	0.15	YES
6	MET	MET	MET	692	0.42	0.17	YES
7	IQSEC3	IQSEC3	IQSEC3	834	0.39	0.19	YES
8	KIT	KIT	KIT	990	0.36	0.21	YES
9	IL2RB	IL2RB	IL2RB	1085	0.35	0.23	YES
10	NTRK1	NTRK1	NTRK1	1124	0.35	0.25	YES
11	CCR5	CCR5	CCR5	1653	0.29	0.24	YES
12	PLD1	PLD1	PLD1	1818	0.27	0.25	YES
13	ACAP1	ACAP1	ACAP1	1873	0.27	0.26	YES
14	HLA-G	HLA-G	HLA-G	1885	0.26	0.28	YES
15	ERBB4	ERBB4	ERBB4	1993	0.26	0.3	YES
16	EHD2	EHD2	EHD2	2425	0.22	0.29	YES
17	EGFR	EGFR	EGFR	2751	0.2	0.28	YES
18	DNM3	DNM3	DNM3	2888	0.2	0.29	YES
19	CXCR1	CXCR1	CXCR1	3005	0.19	0.3	YES
20	HLA-F	HLA-F	HLA-F	3189	0.18	0.3	YES
21	CSF1R	CSF1R	CSF1R	3211	0.18	0.31	YES
22	IL2RG	IL2RG	IL2RG	3243	0.18	0.32	YES
23	GRK5	GRK5	GRK5	3290	0.17	0.33	YES
24	SH3GL2	SH3GL2	SH3GL2	3424	0.17	0.33	YES
25	PARD6G	PARD6G	PARD6G	3494	0.16	0.34	YES
26	ARAP3	ARAP3	ARAP3	3496	0.16	0.35	YES
27	HSPA2	HSPA2	HSPA2	3526	0.16	0.36	YES
28	AGAP2	AGAP2	AGAP2	3546	0.16	0.37	YES
29	PDGFRA	PDGFRA	PDGFRA	3653	0.16	0.38	YES
30	RAB31	RAB31	RAB31	3711	0.15	0.38	YES
31	KDR	KDR	KDR	3810	0.15	0.39	YES
32	CLTCL1	CLTCL1	CLTCL1	3855	0.14	0.39	YES
33	DNM1	DNM1	DNM1	4141	0.13	0.39	YES
34	ASAP1	ASAP1	ASAP1	4205	0.13	0.39	YES
35	HLA-E	HLA-E	HLA-E	4290	0.13	0.4	YES
36	NEDD4	NEDD4	NEDD4	4350	0.12	0.4	YES
37	ARAP2	ARAP2	ARAP2	4372	0.12	0.41	YES
38	TRAF6	TRAF6	TRAF6	4412	0.12	0.42	YES
39	HLA-A	HLA-A	HLA-A	4547	0.11	0.42	YES
40	CXCR4	CXCR4	CXCR4	4575	0.11	0.42	YES
41	TFRC	TFRC	TFRC	4697	0.11	0.42	YES
42	FLT1	FLT1	FLT1	4899	0.1	0.42	YES
43	VPS36	VPS36	VPS36	5257	0.088	0.41	YES
44	PSD	PSD	PSD	5290	0.087	0.41	YES
45	ADRB3	ADRB3	ADRB3	5406	0.084	0.41	YES
46	ASAP3	ASAP3	ASAP3	5434	0.083	0.41	YES
47	ARRB1	ARRB1	ARRB1	5470	0.082	0.42	YES
48	EHD3	EHD3	EHD3	5533	0.08	0.42	YES
49	HLA-B	HLA-B	HLA-B	5542	0.08	0.42	YES
50	FAM125B	FAM125B	FAM125B	5551	0.08	0.43	YES
51	IL2RA	IL2RA	IL2RA	5691	0.076	0.43	YES
52	ARAP1	ARAP1	ARAP1	5750	0.074	0.43	YES
53	RAB11FIP2	RAB11FIP2	RAB11FIP2	5774	0.074	0.43	YES
54	GRK7	GRK7	GRK7	5840	0.072	0.43	YES
55	EHD4	EHD4	EHD4	5994	0.067	0.43	NO
56	IQSEC2	IQSEC2	IQSEC2	6093	0.065	0.43	NO
57	PIP5K1C	PIP5K1C	PIP5K1C	6124	0.064	0.43	NO
58	PLD2	PLD2	PLD2	6222	0.062	0.43	NO
59	SH3KBP1	SH3KBP1	SH3KBP1	6274	0.06	0.43	NO
60	SMURF1	SMURF1	SMURF1	6357	0.058	0.43	NO
61	CBL	CBL	CBL	6489	0.055	0.43	NO
62	VPS37D	VPS37D	VPS37D	6562	0.054	0.43	NO
63	VPS37A	VPS37A	VPS37A	6577	0.053	0.43	NO
64	HLA-C	HLA-C	HLA-C	6831	0.048	0.42	NO
65	VPS4B	VPS4B	VPS4B	6840	0.048	0.42	NO
66	IGF1R	IGF1R	IGF1R	6867	0.047	0.42	NO
67	RET	RET	RET	6951	0.046	0.42	NO
68	LDLR	LDLR	LDLR	6956	0.046	0.43	NO
69	FGFR3	FGFR3	FGFR3	7002	0.045	0.43	NO
70	SH3GLB1	SH3GLB1	SH3GLB1	7260	0.04	0.42	NO
71	ZFYVE20	ZFYVE20	ZFYVE20	7390	0.038	0.41	NO
72	CHMP1B	CHMP1B	CHMP1B	7401	0.038	0.41	NO
73	ADRBK2	ADRBK2	ADRBK2	7407	0.038	0.42	NO
74	SRC	SRC	SRC	7509	0.036	0.41	NO
75	PARD3	PARD3	PARD3	8042	0.028	0.38	NO
76	EPN2	EPN2	EPN2	8064	0.028	0.39	NO
77	CHMP4A	CHMP4A	CHMP4A	8091	0.027	0.39	NO
78	GIT2	GIT2	GIT2	8107	0.027	0.39	NO
79	ACAP2	ACAP2	ACAP2	8162	0.026	0.39	NO
80	CHMP2B	CHMP2B	CHMP2B	8279	0.025	0.38	NO
81	DAB2	DAB2	DAB2	8352	0.024	0.38	NO
82	RAB5C	RAB5C	RAB5C	8561	0.021	0.37	NO
83	EGF	EGF	EGF	8570	0.021	0.37	NO
84	EHD1	EHD1	EHD1	8632	0.02	0.37	NO
85	MDM2	MDM2	MDM2	8702	0.019	0.37	NO
86	EEA1	EEA1	EEA1	8740	0.019	0.36	NO
87	STAM2	STAM2	STAM2	8793	0.018	0.36	NO
88	AP2A1	AP2A1	AP2A1	8834	0.018	0.36	NO
89	HSPA1L	HSPA1L	HSPA1L	8846	0.018	0.36	NO
90	USP8	USP8	USP8	8865	0.017	0.36	NO
91	RAB11FIP5	RAB11FIP5	RAB11FIP5	8945	0.016	0.36	NO
92	ARRB2	ARRB2	ARRB2	9086	0.014	0.35	NO
93	ARFGAP2	ARFGAP2	ARFGAP2	9401	0.011	0.34	NO
94	RAB11B	RAB11B	RAB11B	9486	0.01	0.33	NO
95	VPS24	VPS24	VPS24	9533	0.0094	0.33	NO
96	RAB11FIP1	RAB11FIP1	RAB11FIP1	9596	0.0088	0.33	NO
97	PIKFYVE	PIKFYVE	PIKFYVE	9664	0.0079	0.32	NO
98	RABEP1	RABEP1	RABEP1	9668	0.0078	0.32	NO
99	ITCH	ITCH	ITCH	9782	0.0065	0.32	NO
100	PIP4K2B	PIP4K2B	PIP4K2B	9796	0.0065	0.32	NO
101	HSPA6	HSPA6	HSPA6	9825	0.0062	0.32	NO
102	IQSEC1	IQSEC1	IQSEC1	9914	0.0052	0.31	NO
103	STAM	STAM	STAM	9924	0.0051	0.31	NO
104	AP2B1	AP2B1	AP2B1	10001	0.004	0.31	NO
105	AP2M1	AP2M1	AP2M1	10227	0.0015	0.3	NO
106	CHMP6	CHMP6	CHMP6	10270	0.001	0.3	NO
107	DNAJC6	DNAJC6	DNAJC6	10272	0.001	0.3	NO
108	SMAP1	SMAP1	SMAP1	10374	-0.00023	0.29	NO
109	PDCD6IP	PDCD6IP	PDCD6IP	10411	-0.0006	0.29	NO
110	RAB4A	RAB4A	RAB4A	10420	-0.00071	0.29	NO
111	VPS4A	VPS4A	VPS4A	10427	-0.00081	0.29	NO
112	LDLRAP1	LDLRAP1	LDLRAP1	10474	-0.0012	0.28	NO
113	DNM2	DNM2	DNM2	10487	-0.0013	0.28	NO
114	CHMP4B	CHMP4B	CHMP4B	10502	-0.0015	0.28	NO
115	VTA1	VTA1	VTA1	10516	-0.0016	0.28	NO
116	PRKCI	PRKCI	PRKCI	10528	-0.0018	0.28	NO
117	CDC42	CDC42	CDC42	10545	-0.0019	0.28	NO
118	VPS45	VPS45	VPS45	10591	-0.0023	0.28	NO
119	CHMP5	CHMP5	CHMP5	10641	-0.0028	0.28	NO
120	PSD4	PSD4	PSD4	10749	-0.0039	0.27	NO
121	SMURF2	SMURF2	SMURF2	10767	-0.0041	0.27	NO
122	ASAP2	ASAP2	ASAP2	10778	-0.0042	0.27	NO
123	RUFY1	RUFY1	RUFY1	10850	-0.0049	0.27	NO
124	RAB11FIP4	RAB11FIP4	RAB11FIP4	10923	-0.0056	0.26	NO
125	DNM1L	DNM1L	DNM1L	10930	-0.0056	0.26	NO
126	VPS37B	VPS37B	VPS37B	10979	-0.0061	0.26	NO
127	EPS15	EPS15	EPS15	11160	-0.0079	0.25	NO
128	HSPA1A	HSPA1A	HSPA1A	11281	-0.0094	0.24	NO
129	PRKCZ	PRKCZ	PRKCZ	11295	-0.0096	0.24	NO
130	RAB5B	RAB5B	RAB5B	11394	-0.01	0.24	NO
131	STAMBP	STAMBP	STAMBP	11431	-0.011	0.24	NO
132	SH3GL1	SH3GL1	SH3GL1	11438	-0.011	0.24	NO
133	AP2A2	AP2A2	AP2A2	11522	-0.012	0.24	NO
134	VPS25	VPS25	VPS25	11675	-0.013	0.23	NO
135	RAB22A	RAB22A	RAB22A	11946	-0.016	0.21	NO
136	CLTB	CLTB	CLTB	11978	-0.016	0.21	NO
137	ERBB3	ERBB3	ERBB3	12012	-0.016	0.21	NO
138	EPN3	EPN3	EPN3	12075	-0.017	0.21	NO
139	PSD3	PSD3	PSD3	12088	-0.017	0.21	NO
140	HGS	HGS	HGS	12207	-0.019	0.21	NO
141	ARFGAP3	ARFGAP3	ARFGAP3	12247	-0.019	0.2	NO
142	FGFR4	FGFR4	FGFR4	12285	-0.019	0.2	NO
143	F2R	F2R	F2R	12372	-0.02	0.2	NO
144	CLTC	CLTC	CLTC	12433	-0.021	0.2	NO
145	GRK6	GRK6	GRK6	12479	-0.022	0.2	NO
146	CBLB	CBLB	CBLB	12509	-0.022	0.2	NO
147	GIT1	GIT1	GIT1	12558	-0.022	0.2	NO
148	PIP5K1A	PIP5K1A	PIP5K1A	12689	-0.024	0.19	NO
149	ARFGAP1	ARFGAP1	ARFGAP1	12735	-0.024	0.19	NO
150	RAB5A	RAB5A	RAB5A	12835	-0.026	0.19	NO
151	HSPA1B	HSPA1B	HSPA1B	13078	-0.028	0.18	NO
152	SMAP2	SMAP2	SMAP2	13272	-0.03	0.17	NO
153	CBLC	CBLC	CBLC	13337	-0.031	0.16	NO
154	FAM125A	FAM125A	FAM125A	13470	-0.032	0.16	NO
155	EPN1	EPN1	EPN1	13577	-0.034	0.16	NO
156	RNF41	RNF41	RNF41	13625	-0.034	0.16	NO
157	CHMP2A	CHMP2A	CHMP2A	13685	-0.035	0.16	NO
158	HSPA8	HSPA8	HSPA8	13697	-0.035	0.16	NO
159	SH3GLB2	SH3GLB2	SH3GLB2	13767	-0.036	0.16	NO
160	SNF8	SNF8	SNF8	13856	-0.037	0.15	NO
161	CLTA	CLTA	CLTA	13972	-0.038	0.15	NO
162	TSG101	TSG101	TSG101	14173	-0.04	0.14	NO
163	ADRBK1	ADRBK1	ADRBK1	14288	-0.042	0.14	NO
164	ADRB2	ADRB2	ADRB2	14350	-0.043	0.14	NO
165	ARF6	ARF6	ARF6	14577	-0.046	0.13	NO
166	PARD6B	PARD6B	PARD6B	14586	-0.046	0.13	NO
167	RAB11A	RAB11A	RAB11A	14594	-0.046	0.13	NO
168	VPS28	VPS28	VPS28	14642	-0.046	0.14	NO
169	ACAP3	ACAP3	ACAP3	14763	-0.048	0.13	NO
170	RAB11FIP3	RAB11FIP3	RAB11FIP3	14942	-0.051	0.12	NO
171	WWP1	WWP1	WWP1	14986	-0.052	0.13	NO
172	NEDD4L	NEDD4L	NEDD4L	15794	-0.068	0.086	NO
173	AP2S1	AP2S1	AP2S1	15911	-0.07	0.085	NO
174	AGAP1	AGAP1	AGAP1	16052	-0.074	0.082	NO
175	VPS37C	VPS37C	VPS37C	16132	-0.076	0.083	NO
176	PARD6A	PARD6A	PARD6A	16789	-0.1	0.054	NO
177	ADRB1	ADRB1	ADRB1	17096	-0.12	0.045	NO
178	GRK4	GRK4	GRK4	17209	-0.13	0.048	NO
179	CHMP4C	CHMP4C	CHMP4C	17381	-0.14	0.048	NO

Figure S9. Get High-res Image This plot shows mRNAseq_cNMF expression data heatmap (on the left) a RunningEnrichmentScore(RES) plot (on the top right) and a Signal2Noise(S2N) plot (on the bottom right) of genes in the pathway: BIOCARTA EGF PATHWAY.

Figure S10. Get High-res Image For the top 5 core enriched genes in the pathway: BIOCARTA EGF PATHWAY, this volcano plot shows how much they are up/down-regulated and significant. The significance was calculated by empirical bayesian fit

genes ES table in pathway: BIOCARTA FCER1 PATHWAY

Table S6. Get Full Table This table shows a Running Enrichment Score (RES) of each gene in this pathway, that is, the enrichment score at this point in the ranked list of genes. All genes are ranked by Signal-to-Noise (S2N), a measure of similarity as default and are used to obtain ES matrix of all genes. In this way, GSEA tool uses expression pattern of not only overlapped genes but also not-overlapped genes to produce ES matrix.

Rank	GENE	SYMBOL	DESC	LIST.LOC	S2N	RES	CORE_ENRICHMENT
1	CHP2	CHP2	CHP2	1	1	0.15	YES
2	GRIN2A	GRIN2A	GRIN2A	106	0.67	0.24	YES
3	NOS1	NOS1	NOS1	170	0.61	0.32	YES
4	PRPH2	PRPH2	PRPH2	420	0.5	0.38	YES
5	NEFH	NEFH	NEFH	466	0.48	0.45	YES
6	CASP1	CASP1	CASP1	746	0.41	0.5	YES
7	BCL2	BCL2	BCL2	1377	0.32	0.51	YES
8	GRIA2	GRIA2	GRIA2	1408	0.31	0.55	YES
9	TNF	TNF	TNF	1644	0.29	0.58	YES
10	NEFM	NEFM	NEFM	3249	0.18	0.52	NO
11	GRIN2D	GRIN2D	GRIN2D	3359	0.17	0.54	NO
12	GRIA1	GRIA1	GRIA1	3644	0.16	0.54	NO
13	TNFRSF1B	TNFRSF1B	TNFRSF1B	3859	0.14	0.55	NO
14	NEFL	NEFL	NEFL	4823	0.1	0.51	NO
15	TNFRSF1A	TNFRSF1A	TNFRSF1A	5649	0.077	0.48	NO
16	PRPH	PRPH	PRPH	5986	0.068	0.47	NO
17	CAT	CAT	CAT	6190	0.062	0.47	NO
18	MAP3K5	MAP3K5	MAP3K5	6308	0.06	0.47	NO
19	GRIN2C	GRIN2C	GRIN2C	6529	0.054	0.47	NO
20	PPP3CC	PPP3CC	PPP3CC	6550	0.054	0.47	NO
21	PPP3CB	PPP3CB	PPP3CB	7331	0.039	0.44	NO
22	MAPK14	MAPK14	MAPK14	7767	0.032	0.42	NO
23	MAPK13	MAPK13	MAPK13	7964	0.029	0.41	NO
24	APAF1	APAF1	APAF1	8260	0.025	0.4	NO
25	TP53	TP53	TP53	8348	0.024	0.4	NO
26	CASP9	CASP9	CASP9	8365	0.024	0.4	NO
27	MAPK11	MAPK11	MAPK11	9273	0.012	0.35	NO
28	DAXX	DAXX	DAXX	10330	0.00033	0.29	NO
29	CHP	CHP	CHP	10651	-0.0029	0.28	NO
30	BID	BID	BID	10983	-0.0061	0.26	NO
31	BCL2L1	BCL2L1	BCL2L1	11149	-0.0078	0.25	NO
32	CASP3	CASP3	CASP3	11537	-0.012	0.23	NO
33	MAP2K3	MAP2K3	MAP2K3	11646	-0.013	0.23	NO
34	PPP3R1	PPP3R1	PPP3R1	11767	-0.014	0.22	NO
35	RAC1	RAC1	RAC1	11885	-0.015	0.22	NO
36	CCS	CCS	CCS	11918	-0.016	0.22	NO
37	SLC1A2	SLC1A2	SLC1A2	11985	-0.016	0.22	NO
38	MAP2K6	MAP2K6	MAP2K6	12458	-0.021	0.2	NO
39	DERL1	DERL1	DERL1	12797	-0.025	0.18	NO
40	GPX1	GPX1	GPX1	12812	-0.025	0.18	NO
41	RAB5A	RAB5A	RAB5A	12835	-0.026	0.19	NO
42	GRIN1	GRIN1	GRIN1	13067	-0.028	0.18	NO
43	TOMM40L	TOMM40L	TOMM40L	13230	-0.03	0.17	NO
44	SOD1	SOD1	SOD1	14141	-0.04	0.13	NO
45	BAX	BAX	BAX	15244	-0.057	0.077	NO
46	BAD	BAD	BAD	15633	-0.064	0.065	NO
47	CYCS	CYCS	CYCS	15986	-0.072	0.056	NO
48	TOMM40	TOMM40	TOMM40	16020	-0.073	0.065	NO
49	PPP3CA	PPP3CA	PPP3CA	16237	-0.079	0.064	NO
50	MAPK12	MAPK12	MAPK12	17086	-0.12	0.035	NO
51	PPP3R2	PPP3R2	PPP3R2	17801	-0.2	0.025	NO

Figure S11. Get High-res Image This plot shows mRNAseq_cNMF expression data heatmap (on the left) a RunningEnrichmentScore(RES) plot (on the top right) and a Signal2Noise(S2N) plot (on the bottom right) of genes in the pathway: BIOCARTA FCER1 PATHWAY.

Figure S12. Get High-res Image For the top 5 core enriched genes in the pathway: BIOCARTA FCER1 PATHWAY, this volcano plot shows how much they are up/down-regulated and significant. The significance was calculated by empirical bayesian fit

genes ES table in pathway: BIOCARTA FMLP PATHWAY

Table S7. Get Full Table This table shows a Running Enrichment Score (RES) of each gene in this pathway, that is, the enrichment score at this point in the ranked list of genes. All genes are ranked by Signal-to-Noise (S2N), a measure of similarity as default and are used to obtain ES matrix of all genes. In this way, GSEA tool uses expression pattern of not only overlapped genes but also not-overlapped genes to produce ES matrix.

Rank	GENE	SYMBOL	DESC	LIST.LOC	S2N	RES	CORE_ENRICHMENT
1	PAK7	PAK7	PAK7	4	0.93	0.092	YES
2	NRG2	NRG2	NRG2	5	0.92	0.18	YES
3	NRG1	NRG1	NRG1	18	0.86	0.27	YES
4	PAK3	PAK3	PAK3	398	0.5	0.3	YES
5	PRKCB	PRKCB	PRKCB	798	0.4	0.31	YES
6	PIK3CD	PIK3CD	PIK3CD	1291	0.32	0.32	YES
7	TGFA	TGFA	TGFA	1339	0.32	0.35	YES
8	AREG	AREG	AREG	1582	0.29	0.36	YES
9	PIK3CG	PIK3CG	PIK3CG	1880	0.26	0.37	YES
10	EREG	EREG	EREG	1938	0.26	0.4	YES
11	ERBB4	ERBB4	ERBB4	1993	0.26	0.42	YES
12	SHC3	SHC3	SHC3	2004	0.26	0.44	YES
13	PLCG2	PLCG2	PLCG2	2063	0.25	0.46	YES
14	NRG4	NRG4	NRG4	2260	0.24	0.48	YES
15	PAK6	PAK6	PAK6	2300	0.23	0.5	YES
16	EGFR	EGFR	EGFR	2751	0.2	0.49	YES
17	PRKCA	PRKCA	PRKCA	2960	0.19	0.5	YES
18	HBEGF	HBEGF	HBEGF	3103	0.18	0.51	YES
19	NRG3	NRG3	NRG3	3254	0.18	0.52	YES
20	PIK3R1	PIK3R1	PIK3R1	3640	0.16	0.51	YES
21	STAT5A	STAT5A	STAT5A	3885	0.14	0.51	YES
22	CAMK2A	CAMK2A	CAMK2A	3918	0.14	0.53	YES
23	PAK1	PAK1	PAK1	4017	0.14	0.54	YES
24	BTC	BTC	BTC	4506	0.12	0.52	NO
25	CAMK2G	CAMK2G	CAMK2G	4507	0.12	0.53	NO
26	PIK3R5	PIK3R5	PIK3R5	4684	0.11	0.53	NO
27	CDKN1A	CDKN1A	CDKN1A	5086	0.094	0.52	NO
28	STAT5B	STAT5B	STAT5B	5324	0.086	0.51	NO
29	JUN	JUN	JUN	5675	0.076	0.5	NO
30	GAB1	GAB1	GAB1	6086	0.065	0.49	NO
31	PIK3CA	PIK3CA	PIK3CA	6344	0.059	0.48	NO
32	SHC4	SHC4	SHC4	6407	0.057	0.48	NO
33	CBL	CBL	CBL	6489	0.055	0.48	NO
34	SOS1	SOS1	SOS1	6586	0.053	0.48	NO
35	SOS2	SOS2	SOS2	6925	0.046	0.47	NO
36	CRKL	CRKL	CRKL	7381	0.038	0.45	NO
37	PRKCG	PRKCG	PRKCG	7414	0.038	0.45	NO
38	ARAF	ARAF	ARAF	7500	0.036	0.45	NO
39	SRC	SRC	SRC	7509	0.036	0.45	NO
40	MAPK3	MAPK3	MAPK3	7510	0.036	0.45	NO
41	CRK	CRK	CRK	7526	0.036	0.46	NO
42	ERBB2	ERBB2	ERBB2	7598	0.035	0.46	NO
43	CDKN1B	CDKN1B	CDKN1B	7620	0.034	0.46	NO
44	MAPK10	MAPK10	MAPK10	7764	0.032	0.45	NO
45	CAMK2D	CAMK2D	CAMK2D	7978	0.029	0.44	NO
46	MAPK8	MAPK8	MAPK8	8275	0.025	0.43	NO
47	SHC1	SHC1	SHC1	8477	0.022	0.42	NO
48	EGF	EGF	EGF	8570	0.021	0.42	NO
49	AKT3	AKT3	AKT3	8806	0.018	0.41	NO
50	MAPK1	MAPK1	MAPK1	9197	0.013	0.39	NO
51	MAP2K4	MAP2K4	MAP2K4	9215	0.013	0.39	NO
52	NCK1	NCK1	NCK1	9353	0.012	0.38	NO
53	ABL1	ABL1	ABL1	9540	0.0094	0.37	NO
54	NCK2	NCK2	NCK2	9682	0.0076	0.36	NO
55	PLCG1	PLCG1	PLCG1	9689	0.0076	0.37	NO
56	MAP2K7	MAP2K7	MAP2K7	9779	0.0066	0.36	NO
57	GRB2	GRB2	GRB2	10644	-0.0028	0.31	NO
58	MTOR	MTOR	MTOR	10821	-0.0046	0.3	NO
59	NRAS	NRAS	NRAS	11024	-0.0065	0.3	NO
60	RAF1	RAF1	RAF1	11040	-0.0066	0.29	NO
61	ABL2	ABL2	ABL2	11076	-0.007	0.29	NO
62	AKT2	AKT2	AKT2	11216	-0.0087	0.29	NO
63	KRAS	KRAS	KRAS	11547	-0.012	0.27	NO
64	PAK2	PAK2	PAK2	11588	-0.012	0.27	NO
65	ERBB3	ERBB3	ERBB3	12012	-0.016	0.25	NO
66	PTK2	PTK2	PTK2	12295	-0.02	0.23	NO
67	SHC2	SHC2	SHC2	12319	-0.02	0.23	NO
68	CBLB	CBLB	CBLB	12509	-0.022	0.23	NO
69	AKT1	AKT1	AKT1	12627	-0.023	0.22	NO
70	RPS6KB1	RPS6KB1	RPS6KB1	13084	-0.028	0.2	NO
71	RPS6KB2	RPS6KB2	RPS6KB2	13116	-0.029	0.2	NO
72	MAP2K2	MAP2K2	MAP2K2	13165	-0.029	0.2	NO
73	CBLC	CBLC	CBLC	13337	-0.031	0.19	NO
74	PAK4	PAK4	PAK4	13475	-0.032	0.19	NO
75	PIK3R2	PIK3R2	PIK3R2	13482	-0.032	0.19	NO
76	ELK1	ELK1	ELK1	13526	-0.033	0.19	NO
77	GSK3B	GSK3B	GSK3B	13902	-0.037	0.18	NO
78	PIK3R3	PIK3R3	PIK3R3	14025	-0.039	0.17	NO
79	PIK3CB	PIK3CB	PIK3CB	14073	-0.039	0.18	NO
80	MAP2K1	MAP2K1	MAP2K1	14380	-0.043	0.16	NO
81	MAPK9	MAPK9	MAPK9	14539	-0.045	0.16	NO
82	MYC	MYC	MYC	15261	-0.057	0.12	NO
83	BAD	BAD	BAD	15633	-0.064	0.11	NO
84	BRAF	BRAF	BRAF	16009	-0.073	0.097	NO
85	EIF4EBP1	EIF4EBP1	EIF4EBP1	16737	-0.1	0.066	NO
86	CAMK2B	CAMK2B	CAMK2B	17615	-0.17	0.035	NO

Figure S13. Get High-res Image This plot shows mRNAseq_cNMF expression data heatmap (on the left) a RunningEnrichmentScore(RES) plot (on the top right) and a Signal2Noise(S2N) plot (on the bottom right) of genes in the pathway: BIOCARTA FMLP PATHWAY.

Figure S14. Get High-res Image For the top 5 core enriched genes in the pathway: BIOCARTA FMLP PATHWAY, this volcano plot shows how much they are up/down-regulated and significant. The significance was calculated by empirical bayesian fit

genes ES table in pathway: BIOCARTA GH PATHWAY

Table S8. Get Full Table This table shows a Running Enrichment Score (RES) of each gene in this pathway, that is, the enrichment score at this point in the ranked list of genes. All genes are ranked by Signal-to-Noise (S2N), a measure of similarity as default and are used to obtain ES matrix of all genes. In this way, GSEA tool uses expression pattern of not only overlapped genes but also not-overlapped genes to produce ES matrix.

Rank	GENE	SYMBOL	DESC	LIST.LOC	S2N	RES	CORE_ENRICHMENT
1	PAK7	PAK7	PAK7	4	0.93	0.14	YES
2	PAK3	PAK3	PAK3	398	0.5	0.19	YES
3	MET	MET	MET	692	0.42	0.24	YES
4	PIK3CD	PIK3CD	PIK3CD	1291	0.32	0.26	YES
5	TGFA	TGFA	TGFA	1339	0.32	0.3	YES
6	TGFB3	TGFB3	TGFB3	1575	0.3	0.33	YES
7	PIK3CG	PIK3CG	PIK3CG	1880	0.26	0.36	YES
8	PAK6	PAK6	PAK6	2300	0.23	0.37	YES
9	HGF	HGF	HGF	2713	0.2	0.38	YES
10	EGLN3	EGLN3	EGLN3	2906	0.19	0.4	YES
11	PGF	PGF	PGF	3053	0.18	0.41	YES
12	VEGFA	VEGFA	VEGFA	3410	0.17	0.42	YES
13	EPAS1	EPAS1	EPAS1	3539	0.16	0.44	YES
14	PIK3R1	PIK3R1	PIK3R1	3640	0.16	0.46	YES
15	TGFB2	TGFB2	TGFB2	3888	0.14	0.46	YES
16	PAK1	PAK1	PAK1	4017	0.14	0.48	YES
17	ETS1	ETS1	ETS1	4079	0.14	0.49	YES
18	PIK3R5	PIK3R5	PIK3R5	4684	0.11	0.48	NO
19	TGFB1	TGFB1	TGFB1	4802	0.1	0.49	NO
20	JUN	JUN	JUN	5675	0.076	0.45	NO
21	VEGFC	VEGFC	VEGFC	5755	0.074	0.46	NO
22	GAB1	GAB1	GAB1	6086	0.065	0.45	NO
23	PIK3CA	PIK3CA	PIK3CA	6344	0.059	0.44	NO
24	SOS1	SOS1	SOS1	6586	0.053	0.44	NO
25	SOS2	SOS2	SOS2	6925	0.046	0.43	NO
26	CREBBP	CREBBP	CREBBP	6985	0.045	0.43	NO
27	RAPGEF1	RAPGEF1	RAPGEF1	7004	0.045	0.44	NO
28	CRKL	CRKL	CRKL	7381	0.038	0.42	NO
29	ARAF	ARAF	ARAF	7500	0.036	0.42	NO
30	MAPK3	MAPK3	MAPK3	7510	0.036	0.42	NO
31	CRK	CRK	CRK	7526	0.036	0.43	NO
32	ARNT2	ARNT2	ARNT2	7527	0.036	0.43	NO
33	EGLN2	EGLN2	EGLN2	7531	0.036	0.44	NO
34	RAP1B	RAP1B	RAP1B	7621	0.034	0.44	NO
35	RAP1A	RAP1A	RAP1A	7914	0.03	0.43	NO
36	EP300	EP300	EP300	8075	0.028	0.42	NO
37	SLC2A1	SLC2A1	SLC2A1	8291	0.025	0.42	NO
38	ARNT	ARNT	ARNT	8341	0.024	0.42	NO
39	PTPN11	PTPN11	PTPN11	8456	0.022	0.41	NO
40	AKT3	AKT3	AKT3	8806	0.018	0.4	NO
41	FLCN	FLCN	FLCN	8836	0.018	0.4	NO
42	FIGF	FIGF	FIGF	8862	0.017	0.4	NO
43	MAPK1	MAPK1	MAPK1	9197	0.013	0.38	NO
44	HIF1A	HIF1A	HIF1A	9218	0.013	0.38	NO
45	CUL2	CUL2	CUL2	10003	0.004	0.34	NO
46	PDGFB	PDGFB	PDGFB	10199	0.0018	0.33	NO
47	CDC42	CDC42	CDC42	10545	-0.0019	0.31	NO
48	GRB2	GRB2	GRB2	10644	-0.0028	0.31	NO
49	NRAS	NRAS	NRAS	11024	-0.0065	0.29	NO
50	RAF1	RAF1	RAF1	11040	-0.0066	0.29	NO
51	AKT2	AKT2	AKT2	11216	-0.0087	0.28	NO
52	VEGFB	VEGFB	VEGFB	11544	-0.012	0.26	NO
53	KRAS	KRAS	KRAS	11547	-0.012	0.26	NO
54	PAK2	PAK2	PAK2	11588	-0.012	0.26	NO
55	VHL	VHL	VHL	11749	-0.014	0.26	NO
56	RAC1	RAC1	RAC1	11885	-0.015	0.25	NO
57	EGLN1	EGLN1	EGLN1	12623	-0.023	0.22	NO
58	AKT1	AKT1	AKT1	12627	-0.023	0.22	NO
59	MAP2K2	MAP2K2	MAP2K2	13165	-0.029	0.19	NO
60	PAK4	PAK4	PAK4	13475	-0.032	0.18	NO
61	PIK3R2	PIK3R2	PIK3R2	13482	-0.032	0.19	NO
62	PIK3R3	PIK3R3	PIK3R3	14025	-0.039	0.16	NO
63	PIK3CB	PIK3CB	PIK3CB	14073	-0.039	0.16	NO
64	MAP2K1	MAP2K1	MAP2K1	14380	-0.043	0.16	NO
65	RBX1	RBX1	RBX1	14952	-0.051	0.13	NO
66	TCEB2	TCEB2	TCEB2	15829	-0.069	0.093	NO
67	FH	FH	FH	15907	-0.07	0.1	NO
68	BRAF	BRAF	BRAF	16009	-0.073	0.1	NO
69	TCEB1	TCEB1	TCEB1	17126	-0.12	0.062	NO

Figure S15. Get High-res Image This plot shows mRNAseq_cNMF expression data heatmap (on the left) a RunningEnrichmentScore(RES) plot (on the top right) and a Signal2Noise(S2N) plot (on the bottom right) of genes in the pathway: BIOCARTA GH PATHWAY.

Figure S16. Get High-res Image For the top 5 core enriched genes in the pathway: BIOCARTA GH PATHWAY, this volcano plot shows how much they are up/down-regulated and significant. The significance was calculated by empirical bayesian fit

genes ES table in pathway: BIOCARTA HIVNEF PATHWAY

Table S9. Get Full Table This table shows a Running Enrichment Score (RES) of each gene in this pathway, that is, the enrichment score at this point in the ranked list of genes. All genes are ranked by Signal-to-Noise (S2N), a measure of similarity as default and are used to obtain ES matrix of all genes. In this way, GSEA tool uses expression pattern of not only overlapped genes but also not-overlapped genes to produce ES matrix.

Rank	GENE	SYMBOL	DESC	LIST.LOC	S2N	RES	CORE_ENRICHMENT
1	CALML3	CALML3	CALML3	79	0.71	0.056	YES
2	PPARGC1A	PPARGC1A	PPARGC1A	181	0.61	0.1	YES
3	SLC2A4	SLC2A4	SLC2A4	403	0.5	0.13	YES
4	PYGM	PYGM	PYGM	611	0.44	0.16	YES
5	LIPE	LIPE	LIPE	641	0.43	0.2	YES
6	PPP1R3C	PPP1R3C	PPP1R3C	1159	0.34	0.2	YES
7	GCK	GCK	GCK	1172	0.34	0.22	YES
8	INPP5D	INPP5D	INPP5D	1198	0.34	0.25	YES
9	PIK3CD	PIK3CD	PIK3CD	1291	0.32	0.27	YES
10	PHKG1	PHKG1	PHKG1	1559	0.3	0.28	YES
11	ACACB	ACACB	ACACB	1604	0.29	0.31	YES
12	PCK1	PCK1	PCK1	1698	0.28	0.33	YES
13	SORBS1	SORBS1	SORBS1	1823	0.27	0.34	YES
14	PIK3CG	PIK3CG	PIK3CG	1880	0.26	0.36	YES
15	SHC3	SHC3	SHC3	2004	0.26	0.38	YES
16	SOCS3	SOCS3	SOCS3	2034	0.25	0.4	YES
17	IRS1	IRS1	IRS1	2052	0.25	0.42	YES
18	SOCS1	SOCS1	SOCS1	2210	0.24	0.43	YES
19	GYS2	GYS2	GYS2	2628	0.21	0.42	NO
20	PYGL	PYGL	PYGL	2843	0.2	0.43	NO
21	FOXO1	FOXO1	FOXO1	3197	0.18	0.42	NO
22	IRS4	IRS4	IRS4	3532	0.16	0.42	NO
23	PIK3R1	PIK3R1	PIK3R1	3640	0.16	0.43	NO
24	TRIP10	TRIP10	TRIP10	3854	0.14	0.43	NO
25	PDE3A	PDE3A	PDE3A	4081	0.14	0.43	NO
26	PIK3R5	PIK3R5	PIK3R5	4684	0.11	0.4	NO
27	PPP1R3B	PPP1R3B	PPP1R3B	5006	0.097	0.39	NO
28	PRKAR2A	PRKAR2A	PRKAR2A	5263	0.088	0.39	NO
29	CALM1	CALM1	CALM1	5943	0.069	0.36	NO
30	HK1	HK1	HK1	6085	0.065	0.35	NO
31	PRKAR1B	PRKAR1B	PRKAR1B	6088	0.065	0.36	NO
32	G6PC2	G6PC2	G6PC2	6273	0.06	0.35	NO
33	RPTOR	RPTOR	RPTOR	6331	0.059	0.36	NO
34	PIK3CA	PIK3CA	PIK3CA	6344	0.059	0.36	NO
35	SHC4	SHC4	SHC4	6407	0.057	0.36	NO
36	PYGB	PYGB	PYGB	6420	0.057	0.37	NO
37	MKNK1	MKNK1	MKNK1	6429	0.057	0.37	NO
38	CALML6	CALML6	CALML6	6430	0.057	0.38	NO
39	CBL	CBL	CBL	6489	0.055	0.38	NO
40	SOS1	SOS1	SOS1	6586	0.053	0.38	NO
41	SOS2	SOS2	SOS2	6925	0.046	0.36	NO
42	INSR	INSR	INSR	6978	0.045	0.36	NO
43	RAPGEF1	RAPGEF1	RAPGEF1	7004	0.045	0.36	NO
44	SOCS2	SOCS2	SOCS2	7297	0.04	0.35	NO
45	CRKL	CRKL	CRKL	7381	0.038	0.35	NO
46	ARAF	ARAF	ARAF	7500	0.036	0.35	NO
47	MAPK3	MAPK3	MAPK3	7510	0.036	0.35	NO
48	CRK	CRK	CRK	7526	0.036	0.35	NO
49	FLOT2	FLOT2	FLOT2	7582	0.035	0.35	NO
50	PRKAR1A	PRKAR1A	PRKAR1A	7622	0.034	0.35	NO
51	RHOQ	RHOQ	RHOQ	7650	0.034	0.35	NO
52	PPP1R3D	PPP1R3D	PPP1R3D	7722	0.033	0.35	NO
53	IKBKB	IKBKB	IKBKB	7763	0.032	0.35	NO
54	MAPK10	MAPK10	MAPK10	7764	0.032	0.36	NO
55	PRKAA2	PRKAA2	PRKAA2	8134	0.027	0.34	NO
56	PRKAB1	PRKAB1	PRKAB1	8175	0.026	0.34	NO
57	IRS2	IRS2	IRS2	8181	0.026	0.34	NO
58	CALML5	CALML5	CALML5	8266	0.025	0.34	NO
59	MAPK8	MAPK8	MAPK8	8275	0.025	0.34	NO
60	SHC1	SHC1	SHC1	8477	0.022	0.33	NO
61	HK3	HK3	HK3	8656	0.02	0.32	NO
62	PTPRF	PTPRF	PTPRF	8715	0.019	0.32	NO
63	PTPN1	PTPN1	PTPN1	8739	0.019	0.32	NO
64	PRKX	PRKX	PRKX	8754	0.019	0.32	NO
65	AKT3	AKT3	AKT3	8806	0.018	0.32	NO
66	PRKAB2	PRKAB2	PRKAB2	9073	0.015	0.31	NO
67	MAPK1	MAPK1	MAPK1	9197	0.013	0.3	NO
68	INPP5K	INPP5K	INPP5K	9255	0.013	0.3	NO
69	PRKAG3	PRKAG3	PRKAG3	9670	0.0078	0.28	NO
70	TSC1	TSC1	TSC1	9729	0.0072	0.27	NO
71	PRKACA	PRKACA	PRKACA	9770	0.0066	0.27	NO
72	PRKAR2B	PRKAR2B	PRKAR2B	9800	0.0064	0.27	NO
73	PHKA2	PHKA2	PHKA2	10065	0.0033	0.26	NO
74	SOCS4	SOCS4	SOCS4	10163	0.0022	0.25	NO
75	TSC2	TSC2	TSC2	10456	-0.001	0.24	NO
76	PRKCI	PRKCI	PRKCI	10528	-0.0018	0.23	NO
77	GRB2	GRB2	GRB2	10644	-0.0028	0.23	NO
78	PDPK1	PDPK1	PDPK1	10728	-0.0037	0.22	NO
79	MTOR	MTOR	MTOR	10821	-0.0046	0.22	NO
80	HK2	HK2	HK2	10943	-0.0057	0.21	NO
81	CALM3	CALM3	CALM3	11009	-0.0063	0.21	NO
82	NRAS	NRAS	NRAS	11024	-0.0065	0.21	NO
83	RAF1	RAF1	RAF1	11040	-0.0066	0.21	NO
84	FLOT1	FLOT1	FLOT1	11046	-0.0066	0.21	NO
85	AKT2	AKT2	AKT2	11216	-0.0087	0.2	NO
86	PCK2	PCK2	PCK2	11247	-0.009	0.2	NO
87	GYS1	GYS1	GYS1	11288	-0.0095	0.2	NO
88	PRKCZ	PRKCZ	PRKCZ	11295	-0.0096	0.2	NO
89	EXOC7	EXOC7	EXOC7	11317	-0.0097	0.2	NO
90	KRAS	KRAS	KRAS	11547	-0.012	0.18	NO
91	PHKG2	PHKG2	PHKG2	11617	-0.013	0.18	NO
92	PPP1CB	PPP1CB	PPP1CB	11619	-0.013	0.18	NO
93	MKNK2	MKNK2	MKNK2	11664	-0.013	0.18	NO
94	PRKAG2	PRKAG2	PRKAG2	11798	-0.014	0.18	NO
95	RHEB	RHEB	RHEB	11980	-0.016	0.17	NO
96	SHC2	SHC2	SHC2	12319	-0.02	0.15	NO
97	CALM2	CALM2	CALM2	12360	-0.02	0.15	NO
98	CBLB	CBLB	CBLB	12509	-0.022	0.14	NO
99	AKT1	AKT1	AKT1	12627	-0.023	0.14	NO
100	PRKAA1	PRKAA1	PRKAA1	12703	-0.024	0.14	NO
101	EIF4E2	EIF4E2	EIF4E2	12791	-0.025	0.14	NO
102	PPP1CC	PPP1CC	PPP1CC	12882	-0.026	0.13	NO
103	RPS6KB1	RPS6KB1	RPS6KB1	13084	-0.028	0.12	NO
104	PRKACB	PRKACB	PRKACB	13109	-0.029	0.12	NO
105	RPS6KB2	RPS6KB2	RPS6KB2	13116	-0.029	0.13	NO
106	MAP2K2	MAP2K2	MAP2K2	13165	-0.029	0.13	NO
107	CBLC	CBLC	CBLC	13337	-0.031	0.12	NO
108	PHKA1	PHKA1	PHKA1	13343	-0.031	0.12	NO
109	PIK3R2	PIK3R2	PIK3R2	13482	-0.032	0.12	NO
110	ELK1	ELK1	ELK1	13526	-0.033	0.12	NO
111	EIF4E	EIF4E	EIF4E	13570	-0.034	0.12	NO
112	G6PC	G6PC	G6PC	13655	-0.034	0.12	NO
113	PPP1CA	PPP1CA	PPP1CA	13690	-0.035	0.12	NO
114	PRKAG1	PRKAG1	PRKAG1	13708	-0.035	0.12	NO
115	PHKB	PHKB	PHKB	13730	-0.035	0.12	NO
116	RPS6	RPS6	RPS6	13809	-0.036	0.12	NO
117	GSK3B	GSK3B	GSK3B	13902	-0.037	0.12	NO
118	PIK3R3	PIK3R3	PIK3R3	14025	-0.039	0.12	NO
119	PIK3CB	PIK3CB	PIK3CB	14073	-0.039	0.12	NO
120	MAP2K1	MAP2K1	MAP2K1	14380	-0.043	0.1	NO
121	MAPK9	MAPK9	MAPK9	14539	-0.045	0.098	NO
122	FBP1	FBP1	FBP1	15078	-0.054	0.073	NO
123	BAD	BAD	BAD	15633	-0.064	0.048	NO
124	SREBF1	SREBF1	SREBF1	15879	-0.07	0.04	NO
125	BRAF	BRAF	BRAF	16009	-0.073	0.039	NO
126	PDE3B	PDE3B	PDE3B	16624	-0.095	0.013	NO
127	EIF4EBP1	EIF4EBP1	EIF4EBP1	16737	-0.1	0.016	NO
128	ACACA	ACACA	ACACA	16774	-0.1	0.022	NO
129	FASN	FASN	FASN	16910	-0.11	0.024	NO
130	SH2B2	SH2B2	SH2B2	17407	-0.15	0.0094	NO
131	PKLR	PKLR	PKLR	17784	-0.2	0.0055	NO
132	FBP2	FBP2	FBP2	17972	-0.24	0.016	NO

Figure S17. Get High-res Image This plot shows mRNAseq_cNMF expression data heatmap (on the left) a RunningEnrichmentScore(RES) plot (on the top right) and a Signal2Noise(S2N) plot (on the bottom right) of genes in the pathway: BIOCARTA HIVNEF PATHWAY.

Figure S18. Get High-res Image For the top 5 core enriched genes in the pathway: BIOCARTA HIVNEF PATHWAY, this volcano plot shows how much they are up/down-regulated and significant. The significance was calculated by empirical bayesian fit

genes ES table in pathway: BIOCARTA IL2RB PATHWAY

Table S10. Get Full Table This table shows a Running Enrichment Score (RES) of each gene in this pathway, that is, the enrichment score at this point in the ranked list of genes. All genes are ranked by Signal-to-Noise (S2N), a measure of similarity as default and are used to obtain ES matrix of all genes. In this way, GSEA tool uses expression pattern of not only overlapped genes but also not-overlapped genes to produce ES matrix.

Rank	GENE	SYMBOL	DESC	LIST.LOC	S2N	RES	CORE_ENRICHMENT
1	SCNN1B	SCNN1B	SCNN1B	194	0.6	0.076	YES
2	SCNN1G	SCNN1G	SCNN1G	214	0.59	0.16	YES
3	ATP1A2	ATP1A2	ATP1A2	628	0.44	0.2	YES
4	ATP1A4	ATP1A4	ATP1A4	629	0.44	0.26	YES
5	KCNJ1	KCNJ1	KCNJ1	761	0.4	0.31	YES
6	PRKCB	PRKCB	PRKCB	798	0.4	0.37	YES
7	SCNN1A	SCNN1A	SCNN1A	1021	0.36	0.41	YES
8	ATP1B2	ATP1B2	ATP1B2	1232	0.33	0.44	YES
9	PIK3CD	PIK3CD	PIK3CD	1291	0.32	0.49	YES
10	SGK1	SGK1	SGK1	1630	0.29	0.51	YES
11	PIK3CG	PIK3CG	PIK3CG	1880	0.26	0.53	YES
12	IRS1	IRS1	IRS1	2052	0.25	0.56	YES
13	HSD11B1	HSD11B1	HSD11B1	2393	0.22	0.57	YES
14	SFN	SFN	SFN	2619	0.21	0.59	YES
15	HSD11B2	HSD11B2	HSD11B2	2787	0.2	0.61	YES
16	PRKCA	PRKCA	PRKCA	2960	0.19	0.63	YES
17	ATP1B1	ATP1B1	ATP1B1	3015	0.19	0.65	YES
18	IRS4	IRS4	IRS4	3532	0.16	0.65	YES
19	PIK3R1	PIK3R1	PIK3R1	3640	0.16	0.66	YES
20	NR3C2	NR3C2	NR3C2	4050	0.14	0.66	NO
21	PIK3R5	PIK3R5	PIK3R5	4684	0.11	0.64	NO
22	IGF1	IGF1	IGF1	5515	0.081	0.61	NO
23	PIK3CA	PIK3CA	PIK3CA	6344	0.059	0.57	NO
24	INSR	INSR	INSR	6978	0.045	0.54	NO
25	ATP1A1	ATP1A1	ATP1A1	7293	0.04	0.53	NO
26	PRKCG	PRKCG	PRKCG	7414	0.038	0.53	NO
27	MAPK3	MAPK3	MAPK3	7510	0.036	0.53	NO
28	IRS2	IRS2	IRS2	8181	0.026	0.5	NO
29	MAPK1	MAPK1	MAPK1	9197	0.013	0.44	NO
30	ATP1A3	ATP1A3	ATP1A3	9840	0.006	0.41	NO
31	ATP1B3	ATP1B3	ATP1B3	9957	0.0047	0.4	NO
32	PDPK1	PDPK1	PDPK1	10728	-0.0037	0.36	NO
33	KRAS	KRAS	KRAS	11547	-0.012	0.32	NO
34	PIK3R2	PIK3R2	PIK3R2	13482	-0.032	0.22	NO
35	PIK3R3	PIK3R3	PIK3R3	14025	-0.039	0.19	NO
36	PIK3CB	PIK3CB	PIK3CB	14073	-0.039	0.2	NO
37	FXYD4	FXYD4	FXYD4	14127	-0.04	0.2	NO
38	SLC9A3R2	SLC9A3R2	SLC9A3R2	14716	-0.048	0.17	NO
39	NEDD4L	NEDD4L	NEDD4L	15794	-0.068	0.12	NO
40	ATP1B4	ATP1B4	ATP1B4	16396	-0.085	0.1	NO

Figure S19. Get High-res Image This plot shows mRNAseq_cNMF expression data heatmap (on the left) a RunningEnrichmentScore(RES) plot (on the top right) and a Signal2Noise(S2N) plot (on the bottom right) of genes in the pathway: BIOCARTA IL2RB PATHWAY.

Figure S20. Get High-res Image For the top 5 core enriched genes in the pathway: BIOCARTA IL2RB PATHWAY, this volcano plot shows how much they are up/down-regulated and significant. The significance was calculated by empirical bayesian fit

Fold change

For the top enriched genes, if you want to check whether they are

up-regulated, please check the list of up-regulated genes
down-regulated, please check the list of down-regulated genes

Expression level

For the top enriched genes, if you want to check whether they are

highly expressed genes, please check the list of high (top 30%) expressed genes
low expressed genes, please check the list of low (bottom 30%) expressed genes

An expression pattern of top(30%)/middle(30%)/low(30%) in this subtype against other subtypes is available in a heatmap

Significant gene list

For the top enriched genes, if you want to check whether they are

significantly differently expressed genes by eBayes lm fit, please check the list of significant genes

Subtype clus2 enriched pathways

Table 4. Get Full Table This table shows top 10 pathways which are significantly enriched in cluster clus2. It displays only significant gene sets satisfying nom.p.val.threshold (-1), fwer.p.val.threshold (-1) , fdr.q.val.threshold (0.25) and the default table is sorted by Normalized Enrichment Score (NES). Further details on NES statistics, please visit The Broad GSEA website.

GeneSet(GS)	Size(#genes)	genes.ES.table	ES	NES	NOM.p.val	FDR.q.val	FWER.p.val	Tag..	Gene..	Signal	FDR..median.	glob.p.val
KEGG GLYCOLYSIS GLUCONEOGENESIS	58	genes.ES.table	0.37	1.1	0.27	1	1	0.31	0.17	0.26	0.93	0.45
KEGG FRUCTOSE AND MANNOSE METABOLISM	33	genes.ES.table	0.46	1.5	0.051	0.76	0.9	0.36	0.19	0.3	0.57	0.25
KEGG FATTY ACID METABOLISM	39	genes.ES.table	0.55	1.7	0.018	0.25	0.5	0.56	0.21	0.45	0.11	0.054
KEGG OXIDATIVE PHOSPHORYLATION	114	genes.ES.table	0.45	1.4	0.17	0.7	0.96	0.68	0.28	0.49	0.56	0.22
KEGG PYRIMIDINE METABOLISM	97	genes.ES.table	0.4	1.7	0.018	0.32	0.46	0.28	0.17	0.23	0	0.09
KEGG GLYCINE SERINE AND THREONINE METABOLISM	28	genes.ES.table	0.5	1.4	0.09	0.76	0.97	0.43	0.15	0.36	0.61	0.25
KEGG VALINE LEUCINE AND ISOLEUCINE DEGRADATION	43	genes.ES.table	0.57	1.9	0.016	0.15	0.14	0.58	0.26	0.43	0	0.052
KEGG TYROSINE METABOLISM	39	genes.ES.table	0.42	1.1	0.34	0.89	1	0.56	0.22	0.44	0.8	0.33
KEGG GLUTATHIONE METABOLISM	47	genes.ES.table	0.39	1.1	0.35	0.9	1	0.38	0.18	0.31	0.8	0.33
KEGG AMINO SUGAR AND NUCLEOTIDE SUGAR METABOLISM	42	genes.ES.table	0.32	1.1	0.32	1	1	0.31	0.17	0.26	0.89	0.41

genes ES table in pathway: KEGG GLYCOLYSIS GLUCONEOGENESIS

Table S11. Get Full Table This table shows a Running Enrichment Score (RES) of each gene in this pathway, that is, the enrichment score at this point in the ranked list of genes. All genes are ranked by Signal-to-Noise (S2N), a measure of similarity as default and are used to obtain ES matrix of all genes. In this way, GSEA tool uses expression pattern of not only overlapped genes but also not-overlapped genes to produce ES matrix.

Rank	GENE	SYMBOL	DESC	LIST.LOC	S2N	RES	CORE_ENRICHMENT
1	EHHADH	EHHADH	EHHADH	170	0.32	0.11	YES
2	ACAD8	ACAD8	ACAD8	491	0.22	0.18	YES
3	MCCC2	MCCC2	MCCC2	1083	0.15	0.2	YES
4	ALDH2	ALDH2	ALDH2	1143	0.14	0.25	YES
5	AUH	AUH	AUH	1441	0.12	0.28	YES
6	ABAT	ABAT	ABAT	1495	0.12	0.32	YES
7	ECHS1	ECHS1	ECHS1	1930	0.1	0.34	YES
8	ACAA1	ACAA1	ACAA1	2281	0.088	0.35	YES
9	BCAT2	BCAT2	BCAT2	2478	0.082	0.37	YES
10	ALDH7A1	ALDH7A1	ALDH7A1	2629	0.078	0.39	YES
11	ACAT2	ACAT2	ACAT2	3179	0.064	0.38	YES
12	HSD17B10	HSD17B10	HSD17B10	3226	0.063	0.41	YES
13	ALDH6A1	ALDH6A1	ALDH6A1	3259	0.062	0.43	YES
14	MCEE	MCEE	MCEE	3373	0.06	0.44	YES
15	OXCT1	OXCT1	OXCT1	3573	0.056	0.45	YES
16	MCCC1	MCCC1	MCCC1	3598	0.055	0.47	YES
17	ACAA2	ACAA2	ACAA2	3733	0.053	0.49	YES
18	ALDH3A2	ALDH3A2	ALDH3A2	3771	0.052	0.5	YES
19	ACADSB	ACADSB	ACADSB	3819	0.051	0.52	YES
20	HMGCL	HMGCL	HMGCL	3864	0.05	0.54	YES
21	PCCB	PCCB	PCCB	3962	0.048	0.55	YES
22	DBT	DBT	DBT	4077	0.046	0.56	YES
23	HADH	HADH	HADH	4214	0.044	0.57	YES
24	HIBADH	HIBADH	HIBADH	4541	0.039	0.57	YES
25	PCCA	PCCA	PCCA	4655	0.037	0.57	YES
26	ACADS	ACADS	ACADS	6175	0.018	0.5	NO
27	ACAT1	ACAT1	ACAT1	6431	0.015	0.49	NO
28	HIBCH	HIBCH	HIBCH	6477	0.014	0.49	NO
29	IL4I1	IL4I1	IL4I1	6657	0.012	0.49	NO
30	DLD	DLD	DLD	6677	0.012	0.49	NO
31	IVD	IVD	IVD	6855	0.01	0.48	NO
32	ALDH1B1	ALDH1B1	ALDH1B1	7281	0.0055	0.46	NO
33	BCKDHA	BCKDHA	BCKDHA	7417	0.0036	0.46	NO
34	MUT	MUT	MUT	7582	0.0021	0.45	NO
35	HMGCS1	HMGCS1	HMGCS1	8183	-0.0047	0.42	NO
36	HADHA	HADHA	HADHA	8203	-0.0049	0.42	NO
37	HADHB	HADHB	HADHB	8593	-0.0089	0.4	NO
38	ACADM	ACADM	ACADM	8743	-0.01	0.4	NO
39	HMGCS2	HMGCS2	HMGCS2	9190	-0.015	0.38	NO
40	BCKDHB	BCKDHB	BCKDHB	10550	-0.03	0.31	NO
41	ALDH9A1	ALDH9A1	ALDH9A1	10754	-0.033	0.31	NO
42	OXCT2	OXCT2	OXCT2	13542	-0.072	0.19	NO
43	AOX1	AOX1	AOX1	16679	-0.19	0.087	NO

Figure S21. Get High-res Image This plot shows mRNAseq_cNMF expression data heatmap (on the left) a RunningEnrichmentScore(RES) plot (on the top right) and a Signal2Noise(S2N) plot (on the bottom right) of genes in the pathway: KEGG GLYCOLYSIS GLUCONEOGENESIS.

Figure S22. Get High-res Image For the top 5 core enriched genes in the pathway: KEGG GLYCOLYSIS GLUCONEOGENESIS, this volcano plot shows how much they are up/down-regulated and significant. The significance was calculated by empirical bayesian fit

genes ES table in pathway: KEGG FRUCTOSE AND MANNOSE METABOLISM

Table S12. Get Full Table This table shows a Running Enrichment Score (RES) of each gene in this pathway, that is, the enrichment score at this point in the ranked list of genes. All genes are ranked by Signal-to-Noise (S2N), a measure of similarity as default and are used to obtain ES matrix of all genes. In this way, GSEA tool uses expression pattern of not only overlapped genes but also not-overlapped genes to produce ES matrix.

Rank	GENE	SYMBOL	DESC	LIST.LOC	S2N	RES	CORE_ENRICHMENT
1	PRIM2	PRIM2	PRIM2	191	0.32	0.041	YES
2	NME5	NME5	NME5	497	0.22	0.06	YES
3	NT5M	NT5M	NT5M	532	0.22	0.093	YES
4	NT5C	NT5C	NT5C	534	0.21	0.13	YES
5	NT5C1A	NT5C1A	NT5C1A	556	0.21	0.16	YES
6	UPP2	UPP2	UPP2	586	0.21	0.19	YES
7	UPB1	UPB1	UPB1	656	0.2	0.22	YES
8	POLE2	POLE2	POLE2	802	0.18	0.24	YES
9	POLD4	POLD4	POLD4	1062	0.15	0.25	YES
10	TK1	TK1	TK1	1274	0.13	0.26	YES
11	NT5C3	NT5C3	NT5C3	1329	0.13	0.28	YES
12	ENTPD8	ENTPD8	ENTPD8	1885	0.1	0.26	YES
13	POLE4	POLE4	POLE4	1962	0.099	0.28	YES
14	RRM2	RRM2	RRM2	1963	0.099	0.29	YES
15	POLR2J	POLR2J	POLR2J	2126	0.093	0.3	YES
16	TXNRD2	TXNRD2	TXNRD2	2216	0.09	0.31	YES
17	DTYMK	DTYMK	DTYMK	2244	0.089	0.32	YES
18	CDA	CDA	CDA	2369	0.085	0.33	YES
19	NME1	NME1	NME1	2560	0.079	0.33	YES
20	POLR3K	POLR3K	POLR3K	2610	0.078	0.34	YES
21	POLR2F	POLR2F	POLR2F	2822	0.073	0.34	YES
22	ITPA	ITPA	ITPA	2832	0.072	0.35	YES
23	POLR2I	POLR2I	POLR2I	2863	0.072	0.36	YES
24	POLR2L	POLR2L	POLR2L	2892	0.071	0.37	YES
25	DPYS	DPYS	DPYS	3006	0.068	0.38	YES
26	PNP	PNP	PNP	3037	0.068	0.39	YES
27	POLR2K	POLR2K	POLR2K	3079	0.066	0.4	YES
28	POLD2	POLD2	POLD2	3637	0.055	0.37	NO
29	DHODH	DHODH	DHODH	3845	0.051	0.37	NO
30	POLR2G	POLR2G	POLR2G	3951	0.049	0.37	NO
31	ENTPD6	ENTPD6	ENTPD6	4084	0.046	0.37	NO
32	POLR2H	POLR2H	POLR2H	4115	0.046	0.38	NO
33	NME1-NME2	NME1-NME2	NME1-NME2	4151	0.045	0.38	NO
34	POLR1E	POLR1E	POLR1E	4322	0.042	0.38	NO
35	NME2	NME2	NME2	4440	0.04	0.38	NO
36	POLR1C	POLR1C	POLR1C	4608	0.038	0.38	NO
37	POLR3H	POLR3H	POLR3H	5072	0.032	0.36	NO
38	POLR2E	POLR2E	POLR2E	5077	0.032	0.36	NO
39	NUDT2	NUDT2	NUDT2	5087	0.032	0.37	NO
40	NT5C2	NT5C2	NT5C2	5125	0.031	0.37	NO
41	PNPT1	PNPT1	PNPT1	5290	0.029	0.37	NO
42	UCK1	UCK1	UCK1	5307	0.028	0.37	NO
43	NME3	NME3	NME3	5474	0.026	0.36	NO
44	UPP1	UPP1	UPP1	5668	0.024	0.36	NO
45	POLR1D	POLR1D	POLR1D	5812	0.022	0.35	NO
46	POLR3D	POLR3D	POLR3D	5866	0.021	0.35	NO
47	ENTPD1	ENTPD1	ENTPD1	6176	0.018	0.34	NO
48	RRM2B	RRM2B	RRM2B	6681	0.012	0.31	NO
49	NME6	NME6	NME6	6711	0.012	0.32	NO
50	CANT1	CANT1	CANT1	6802	0.011	0.31	NO
51	CMPK2	CMPK2	CMPK2	6844	0.01	0.31	NO
52	CTPS2	CTPS2	CTPS2	6949	0.009	0.31	NO
53	ZNRD1	ZNRD1	ZNRD1	7066	0.0077	0.3	NO
54	UMPS	UMPS	UMPS	7319	0.0049	0.29	NO
55	POLR2J3	POLR2J3	POLR2J3	7656	0.0012	0.27	NO
56	DCK	DCK	DCK	7782	-0.00038	0.26	NO
57	NME4	NME4	NME4	7834	-0.00093	0.26	NO
58	DCTD	DCTD	DCTD	7935	-0.0022	0.26	NO
59	POLR3C	POLR3C	POLR3C	7941	-0.0022	0.26	NO
60	POLR3B	POLR3B	POLR3B	8072	-0.0036	0.25	NO
61	RRM1	RRM1	RRM1	8201	-0.0049	0.24	NO
62	CMPK1	CMPK1	CMPK1	8391	-0.0068	0.23	NO
63	UCK2	UCK2	UCK2	8567	-0.0087	0.22	NO
64	POLR2J2	POLR2J2	POLR2J2	8683	-0.0099	0.22	NO
65	TK2	TK2	TK2	8758	-0.011	0.22	NO
66	NME7	NME7	NME7	9009	-0.013	0.21	NO
67	UPRT	UPRT	UPRT	9034	-0.013	0.21	NO
68	POLA2	POLA2	POLA2	9041	-0.013	0.21	NO
69	POLR3GL	POLR3GL	POLR3GL	9227	-0.015	0.2	NO
70	AK3	AK3	AK3	9296	-0.016	0.2	NO
71	POLE	POLE	POLE	9417	-0.018	0.2	NO
72	POLD1	POLD1	POLD1	9460	-0.018	0.2	NO
73	TYMS	TYMS	TYMS	9551	-0.019	0.2	NO
74	POLR3F	POLR3F	POLR3F	9829	-0.022	0.18	NO
75	TXNRD1	TXNRD1	TXNRD1	10232	-0.027	0.17	NO
76	POLR2C	POLR2C	POLR2C	10458	-0.029	0.16	NO
77	POLE3	POLE3	POLE3	10685	-0.032	0.15	NO
78	POLR2A	POLR2A	POLR2A	10821	-0.033	0.15	NO
79	DUT	DUT	DUT	10848	-0.034	0.15	NO
80	UCKL1	UCKL1	UCKL1	10851	-0.034	0.16	NO
81	ENTPD5	ENTPD5	ENTPD5	10998	-0.035	0.16	NO
82	POLR3A	POLR3A	POLR3A	11004	-0.036	0.16	NO
83	POLR1A	POLR1A	POLR1A	11124	-0.037	0.16	NO
84	POLD3	POLD3	POLD3	11380	-0.04	0.15	NO
85	POLR2B	POLR2B	POLR2B	11586	-0.043	0.15	NO
86	POLA1	POLA1	POLA1	11631	-0.043	0.15	NO
87	POLR2D	POLR2D	POLR2D	11790	-0.045	0.15	NO
88	POLR1B	POLR1B	POLR1B	11974	-0.048	0.15	NO
89	ENTPD4	ENTPD4	ENTPD4	12548	-0.056	0.13	NO
90	TYMP	TYMP	TYMP	13084	-0.064	0.11	NO
91	PRIM1	PRIM1	PRIM1	13725	-0.076	0.085	NO
92	CAD	CAD	CAD	14115	-0.084	0.078	NO
93	NT5E	NT5E	NT5E	15098	-0.11	0.042	NO
94	DPYD	DPYD	DPYD	15323	-0.12	0.049	NO
95	ENTPD3	ENTPD3	ENTPD3	15975	-0.15	0.037	NO
96	NT5C1B	NT5C1B	NT5C1B	16772	-0.2	0.025	NO
97	POLR3G	POLR3G	POLR3G	17870	-0.35	0.021	NO

Figure S23. Get High-res Image This plot shows mRNAseq_cNMF expression data heatmap (on the left) a RunningEnrichmentScore(RES) plot (on the top right) and a Signal2Noise(S2N) plot (on the bottom right) of genes in the pathway: KEGG FRUCTOSE AND MANNOSE METABOLISM.

Figure S24. Get High-res Image For the top 5 core enriched genes in the pathway: KEGG FRUCTOSE AND MANNOSE METABOLISM, this volcano plot shows how much they are up/down-regulated and significant. The significance was calculated by empirical bayesian fit

genes ES table in pathway: KEGG FATTY ACID METABOLISM

Table S13. Get Full Table This table shows a Running Enrichment Score (RES) of each gene in this pathway, that is, the enrichment score at this point in the ranked list of genes. All genes are ranked by Signal-to-Noise (S2N), a measure of similarity as default and are used to obtain ES matrix of all genes. In this way, GSEA tool uses expression pattern of not only overlapped genes but also not-overlapped genes to produce ES matrix.

Rank	GENE	SYMBOL	DESC	LIST.LOC	S2N	RES	CORE_ENRICHMENT
1	ACADL	ACADL	ACADL	79	0.4	0.1	YES
2	EHHADH	EHHADH	EHHADH	170	0.32	0.19	YES
3	ADH1C	ADH1C	ADH1C	196	0.31	0.27	YES
4	ADH1B	ADH1B	ADH1B	658	0.2	0.3	YES
5	ADH1A	ADH1A	ADH1A	1026	0.15	0.32	YES
6	ALDH2	ALDH2	ALDH2	1143	0.14	0.36	YES
7	ADH6	ADH6	ADH6	1741	0.11	0.36	YES
8	ECHS1	ECHS1	ECHS1	1930	0.1	0.37	YES
9	ADH4	ADH4	ADH4	2199	0.09	0.38	YES
10	ACAA1	ACAA1	ACAA1	2281	0.088	0.4	YES
11	ACOX3	ACOX3	ACOX3	2318	0.087	0.42	YES
12	DCI	DCI	DCI	2321	0.087	0.45	YES
13	PECI	PECI	PECI	2364	0.085	0.47	YES
14	CPT1B	CPT1B	CPT1B	2365	0.085	0.49	YES
15	ALDH7A1	ALDH7A1	ALDH7A1	2629	0.078	0.5	YES
16	GCDH	GCDH	GCDH	2894	0.071	0.51	YES
17	ACSL6	ACSL6	ACSL6	3070	0.067	0.51	YES
18	ADH5	ADH5	ADH5	3133	0.066	0.53	YES
19	ACAT2	ACAT2	ACAT2	3179	0.064	0.54	YES
20	ACAA2	ACAA2	ACAA2	3733	0.053	0.53	YES
21	ALDH3A2	ALDH3A2	ALDH3A2	3771	0.052	0.54	YES
22	ACADSB	ACADSB	ACADSB	3819	0.051	0.55	YES
23	HADH	HADH	HADH	4214	0.044	0.54	NO
24	CPT2	CPT2	CPT2	4708	0.037	0.53	NO
25	ACADVL	ACADVL	ACADVL	5218	0.03	0.51	NO
26	ACSL1	ACSL1	ACSL1	5965	0.02	0.47	NO
27	ACADS	ACADS	ACADS	6175	0.018	0.46	NO
28	ACAT1	ACAT1	ACAT1	6431	0.015	0.45	NO
29	CYP4A11	CYP4A11	CYP4A11	6620	0.013	0.45	NO
30	ALDH1B1	ALDH1B1	ALDH1B1	7281	0.0055	0.41	NO
31	HADHA	HADHA	HADHA	8203	-0.0049	0.36	NO
32	HADHB	HADHB	HADHB	8593	-0.0089	0.34	NO
33	ACADM	ACADM	ACADM	8743	-0.01	0.34	NO
34	ALDH9A1	ALDH9A1	ALDH9A1	10754	-0.033	0.24	NO
35	ACSL3	ACSL3	ACSL3	12894	-0.061	0.14	NO
36	CPT1A	CPT1A	CPT1A	14404	-0.092	0.08	NO
37	ACSL4	ACSL4	ACSL4	14634	-0.098	0.095	NO
38	CPT1C	CPT1C	CPT1C	15579	-0.13	0.079	NO
39	ACSL5	ACSL5	ACSL5	17297	-0.25	0.053	NO

Figure S25. Get High-res Image This plot shows mRNAseq_cNMF expression data heatmap (on the left) a RunningEnrichmentScore(RES) plot (on the top right) and a Signal2Noise(S2N) plot (on the bottom right) of genes in the pathway: KEGG FATTY ACID METABOLISM.

Figure S26. Get High-res Image For the top 5 core enriched genes in the pathway: KEGG FATTY ACID METABOLISM, this volcano plot shows how much they are up/down-regulated and significant. The significance was calculated by empirical bayesian fit

genes ES table in pathway: KEGG OXIDATIVE PHOSPHORYLATION

Table S14. Get Full Table This table shows a Running Enrichment Score (RES) of each gene in this pathway, that is, the enrichment score at this point in the ranked list of genes. All genes are ranked by Signal-to-Noise (S2N), a measure of similarity as default and are used to obtain ES matrix of all genes. In this way, GSEA tool uses expression pattern of not only overlapped genes but also not-overlapped genes to produce ES matrix.

Rank	GENE	SYMBOL	DESC	LIST.LOC	S2N	RES	CORE_ENRICHMENT
1	PFKFB1	PFKFB1	PFKFB1	96	0.38	0.16	YES
2	GMDS	GMDS	GMDS	828	0.17	0.2	YES
3	PFKFB4	PFKFB4	PFKFB4	1048	0.15	0.25	YES
4	FBP2	FBP2	FBP2	1347	0.13	0.29	YES
5	AKR1B10	AKR1B10	AKR1B10	1363	0.13	0.34	YES
6	PMM1	PMM1	PMM1	1887	0.1	0.36	YES
7	KHK	KHK	KHK	2270	0.088	0.38	YES
8	HK3	HK3	HK3	2733	0.075	0.38	YES
9	HK2	HK2	HK2	2941	0.07	0.4	YES
10	PHPT1	PHPT1	PHPT1	3090	0.066	0.42	YES
11	GMPPA	GMPPA	GMPPA	3180	0.064	0.45	YES
12	SORD	SORD	SORD	3466	0.058	0.46	YES
13	MPI	MPI	MPI	4272	0.043	0.43	NO
14	PFKFB2	PFKFB2	PFKFB2	4583	0.038	0.43	NO
15	MTMR2	MTMR2	MTMR2	5022	0.032	0.42	NO
16	PMM2	PMM2	PMM2	5026	0.032	0.44	NO
17	TPI1	TPI1	TPI1	5295	0.029	0.43	NO
18	GMPPB	GMPPB	GMPPB	5818	0.022	0.42	NO
19	PFKL	PFKL	PFKL	6463	0.014	0.39	NO
20	FUK	FUK	FUK	6865	0.01	0.37	NO
21	MTMR7	MTMR7	MTMR7	7310	0.005	0.35	NO
22	MTMR6	MTMR6	MTMR6	7699	0.00071	0.33	NO
23	AKR1B1	AKR1B1	AKR1B1	7837	-0.00096	0.32	NO
24	HK1	HK1	HK1	9279	-0.016	0.25	NO
25	MTMR1	MTMR1	MTMR1	9683	-0.021	0.23	NO
26	ALDOC	ALDOC	ALDOC	9886	-0.023	0.23	NO
27	PFKP	PFKP	PFKP	10609	-0.031	0.21	NO
28	FPGT	FPGT	FPGT	10773	-0.033	0.21	NO
29	FBP1	FBP1	FBP1	11479	-0.041	0.19	NO
30	TSTA3	TSTA3	TSTA3	11713	-0.044	0.2	NO
31	ALDOB	ALDOB	ALDOB	14291	-0.089	0.095	NO
32	PFKM	PFKM	PFKM	15474	-0.13	0.085	NO
33	PFKFB3	PFKFB3	PFKFB3	16091	-0.15	0.12	NO

Figure S27. Get High-res Image This plot shows mRNAseq_cNMF expression data heatmap (on the left) a RunningEnrichmentScore(RES) plot (on the top right) and a Signal2Noise(S2N) plot (on the bottom right) of genes in the pathway: KEGG OXIDATIVE PHOSPHORYLATION.

Figure S28. Get High-res Image For the top 5 core enriched genes in the pathway: KEGG OXIDATIVE PHOSPHORYLATION, this volcano plot shows how much they are up/down-regulated and significant. The significance was calculated by empirical bayesian fit

genes ES table in pathway: KEGG PYRIMIDINE METABOLISM

Table S15. Get Full Table This table shows a Running Enrichment Score (RES) of each gene in this pathway, that is, the enrichment score at this point in the ranked list of genes. All genes are ranked by Signal-to-Noise (S2N), a measure of similarity as default and are used to obtain ES matrix of all genes. In this way, GSEA tool uses expression pattern of not only overlapped genes but also not-overlapped genes to produce ES matrix.

Rank	GENE	SYMBOL	DESC	LIST.LOC	S2N	RES	CORE_ENRICHMENT
1	ACSM1	ACSM1	ACSM1	901	0.16	0.044	YES
2	ALDH2	ALDH2	ALDH2	1143	0.14	0.11	YES
3	AKR1B10	AKR1B10	AKR1B10	1363	0.13	0.17	YES
4	ABAT	ABAT	ABAT	1495	0.12	0.23	YES
5	ACSM5	ACSM5	ACSM5	1613	0.11	0.29	YES
6	ECHS1	ECHS1	ECHS1	1930	0.1	0.33	YES
7	BDH1	BDH1	BDH1	2317	0.087	0.36	YES
8	ALDH7A1	ALDH7A1	ALDH7A1	2629	0.078	0.39	YES
9	ACAT2	ACAT2	ACAT2	3179	0.064	0.39	YES
10	OXCT1	OXCT1	OXCT1	3573	0.056	0.4	YES
11	ALDH3A2	ALDH3A2	ALDH3A2	3771	0.052	0.42	YES
12	HMGCL	HMGCL	HMGCL	3864	0.05	0.44	YES
13	HADH	HADH	HADH	4214	0.044	0.45	YES
14	BDH2	BDH2	BDH2	4217	0.044	0.48	YES
15	L2HGDH	L2HGDH	L2HGDH	5559	0.026	0.42	NO
16	AACS	AACS	AACS	5897	0.021	0.41	NO
17	ACADS	ACADS	ACADS	6175	0.018	0.4	NO
18	ACAT1	ACAT1	ACAT1	6431	0.015	0.4	NO
19	PDHB	PDHB	PDHB	6561	0.014	0.4	NO
20	ALDH1B1	ALDH1B1	ALDH1B1	7281	0.0055	0.36	NO
21	PDHA1	PDHA1	PDHA1	8178	-0.0046	0.32	NO
22	HMGCS1	HMGCS1	HMGCS1	8183	-0.0047	0.32	NO
23	HADHA	HADHA	HADHA	8203	-0.0049	0.32	NO
24	ACSM2A	ACSM2A	ACSM2A	8901	-0.012	0.29	NO
25	HMGCS2	HMGCS2	HMGCS2	9190	-0.015	0.28	NO
26	ACSM3	ACSM3	ACSM3	10319	-0.028	0.24	NO
27	ALDH9A1	ALDH9A1	ALDH9A1	10754	-0.033	0.23	NO
28	ALDH5A1	ALDH5A1	ALDH5A1	11386	-0.04	0.22	NO
29	OXCT2	OXCT2	OXCT2	13542	-0.072	0.14	NO
30	GAD1	GAD1	GAD1	16926	-0.21	0.073	NO

Figure S29. Get High-res Image This plot shows mRNAseq_cNMF expression data heatmap (on the left) a RunningEnrichmentScore(RES) plot (on the top right) and a Signal2Noise(S2N) plot (on the bottom right) of genes in the pathway: KEGG PYRIMIDINE METABOLISM.

Figure S30. Get High-res Image For the top 5 core enriched genes in the pathway: KEGG PYRIMIDINE METABOLISM, this volcano plot shows how much they are up/down-regulated and significant. The significance was calculated by empirical bayesian fit

genes ES table in pathway: KEGG GLYCINE SERINE AND THREONINE METABOLISM

Table S16. Get Full Table This table shows a Running Enrichment Score (RES) of each gene in this pathway, that is, the enrichment score at this point in the ranked list of genes. All genes are ranked by Signal-to-Noise (S2N), a measure of similarity as default and are used to obtain ES matrix of all genes. In this way, GSEA tool uses expression pattern of not only overlapped genes but also not-overlapped genes to produce ES matrix.

Rank	GENE	SYMBOL	DESC	LIST.LOC	S2N	RES	CORE_ENRICHMENT
1	SLC6A3	SLC6A3	SLC6A3	135	0.35	0.039	YES
2	COX6A2	COX6A2	COX6A2	292	0.28	0.068	YES
3	COX4I2	COX4I2	COX4I2	366	0.25	0.098	YES
4	SNCA	SNCA	SNCA	964	0.16	0.086	YES
5	NDUFA4L2	NDUFA4L2	NDUFA4L2	1067	0.15	0.1	YES
6	NDUFA3	NDUFA3	NDUFA3	1471	0.12	0.095	YES
7	COX6C	COX6C	COX6C	1749	0.11	0.094	YES
8	NDUFS8	NDUFS8	NDUFS8	1827	0.1	0.1	YES
9	NDUFB1	NDUFB1	NDUFB1	1891	0.1	0.11	YES
10	COX6A1	COX6A1	COX6A1	1936	0.1	0.12	YES
11	NDUFB9	NDUFB9	NDUFB9	1949	0.1	0.14	YES
12	UQCR11	UQCR11	UQCR11	1952	0.1	0.15	YES
13	NDUFB7	NDUFB7	NDUFB7	1970	0.099	0.16	YES
14	NDUFA2	NDUFA2	NDUFA2	1995	0.098	0.18	YES
15	COX5B	COX5B	COX5B	2015	0.098	0.19	YES
16	ATP5D	ATP5D	ATP5D	2280	0.088	0.18	YES
17	NDUFA7	NDUFA7	NDUFA7	2326	0.086	0.19	YES
18	NDUFC2	NDUFC2	NDUFC2	2374	0.085	0.2	YES
19	UQCR10	UQCR10	UQCR10	2381	0.085	0.21	YES
20	COX7B	COX7B	COX7B	2412	0.084	0.22	YES
21	COX8C	COX8C	COX8C	2507	0.081	0.23	YES
22	GPR37	GPR37	GPR37	2510	0.081	0.24	YES
23	UQCRB	UQCRB	UQCRB	2516	0.08	0.25	YES
24	NDUFA1	NDUFA1	NDUFA1	2572	0.079	0.26	YES
25	COX7A1	COX7A1	COX7A1	2625	0.078	0.26	YES
26	COX8A	COX8A	COX8A	2687	0.076	0.27	YES
27	NDUFB10	NDUFB10	NDUFB10	2698	0.076	0.28	YES
28	UQCRQ	UQCRQ	UQCRQ	2736	0.075	0.29	YES
29	ATP5E	ATP5E	ATP5E	2845	0.072	0.29	YES
30	TH	TH	TH	2868	0.072	0.3	YES
31	NDUFB8	NDUFB8	NDUFB8	2878	0.071	0.31	YES
32	NDUFV3	NDUFV3	NDUFV3	2904	0.071	0.32	YES
33	NDUFB3	NDUFB3	NDUFB3	2923	0.07	0.33	YES
34	NDUFV2	NDUFV2	NDUFV2	2930	0.07	0.34	YES
35	ATP5G1	ATP5G1	ATP5G1	2959	0.069	0.34	YES
36	COX6B1	COX6B1	COX6B1	2997	0.068	0.35	YES
37	NDUFS6	NDUFS6	NDUFS6	3015	0.068	0.36	YES
38	NDUFB6	NDUFB6	NDUFB6	3053	0.067	0.37	YES
39	NDUFS7	NDUFS7	NDUFS7	3217	0.063	0.37	YES
40	PINK1	PINK1	PINK1	3218	0.063	0.37	YES
41	NDUFV1	NDUFV1	NDUFV1	3399	0.059	0.37	YES
42	NDUFA8	NDUFA8	NDUFA8	3475	0.058	0.38	YES
43	COX4I1	COX4I1	COX4I1	3566	0.056	0.38	YES
44	COX5A	COX5A	COX5A	3655	0.054	0.38	YES
45	NDUFB2	NDUFB2	NDUFB2	3664	0.054	0.39	YES
46	UQCRHL	UQCRHL	UQCRHL	3675	0.054	0.39	YES
47	UBB	UBB	UBB	3886	0.05	0.39	YES
48	NDUFC1	NDUFC1	NDUFC1	3937	0.049	0.39	YES
49	UBE2G2	UBE2G2	UBE2G2	4060	0.047	0.39	YES
50	NDUFAB1	NDUFAB1	NDUFAB1	4062	0.047	0.4	YES
51	PARK7	PARK7	PARK7	4210	0.044	0.4	YES
52	UQCRH	UQCRH	UQCRH	4294	0.043	0.4	YES
53	SLC25A4	SLC25A4	SLC25A4	4340	0.042	0.4	YES
54	COX7A2	COX7A2	COX7A2	4400	0.041	0.4	YES
55	NDUFA9	NDUFA9	NDUFA9	4511	0.039	0.4	YES
56	NDUFA6	NDUFA6	NDUFA6	4683	0.037	0.4	YES
57	UBE2L3	UBE2L3	UBE2L3	4749	0.036	0.4	YES
58	VDAC3	VDAC3	VDAC3	4788	0.036	0.4	YES
59	ATP5O	ATP5O	ATP5O	4853	0.035	0.4	YES
60	ATP5J	ATP5J	ATP5J	4858	0.035	0.41	YES
61	NDUFA5	NDUFA5	NDUFA5	4881	0.034	0.41	YES
62	NDUFS5	NDUFS5	NDUFS5	4895	0.034	0.42	YES
63	COX7C	COX7C	COX7C	4976	0.033	0.42	YES
64	NDUFA10	NDUFA10	NDUFA10	5048	0.032	0.42	YES
65	CYC1	CYC1	CYC1	5076	0.032	0.42	YES
66	UQCRC1	UQCRC1	UQCRC1	5089	0.032	0.42	YES
67	ATP5H	ATP5H	ATP5H	5197	0.03	0.42	YES
68	NDUFA4	NDUFA4	NDUFA4	5212	0.03	0.42	YES
69	CYCS	CYCS	CYCS	5312	0.028	0.42	NO
70	NDUFS3	NDUFS3	NDUFS3	5422	0.027	0.42	NO
71	NDUFB4	NDUFB4	NDUFB4	5558	0.026	0.42	NO
72	ATP5C1	ATP5C1	ATP5C1	5570	0.025	0.42	NO
73	UBA1	UBA1	UBA1	5658	0.024	0.42	NO
74	VDAC1	VDAC1	VDAC1	5684	0.024	0.42	NO
75	COX7A2L	COX7A2L	COX7A2L	5918	0.021	0.41	NO
76	ATP5G2	ATP5G2	ATP5G2	6100	0.019	0.4	NO
77	SDHB	SDHB	SDHB	6356	0.016	0.39	NO
78	NDUFB5	NDUFB5	NDUFB5	6438	0.015	0.39	NO
79	SDHA	SDHA	SDHA	6455	0.015	0.39	NO
80	HTRA2	HTRA2	HTRA2	6622	0.013	0.38	NO
81	UQCRFS1	UQCRFS1	UQCRFS1	6707	0.012	0.38	NO
82	NDUFS4	NDUFS4	NDUFS4	6821	0.011	0.37	NO
83	NDUFS2	NDUFS2	NDUFS2	6910	0.0094	0.37	NO
84	ATP5G3	ATP5G3	ATP5G3	6990	0.0085	0.36	NO
85	ATP5A1	ATP5A1	ATP5A1	7015	0.0083	0.36	NO
86	UBE2J2	UBE2J2	UBE2J2	7026	0.0081	0.36	NO
87	SDHC	SDHC	SDHC	7055	0.0078	0.36	NO
88	VDAC2	VDAC2	VDAC2	7212	0.0062	0.36	NO
89	ATP5B	ATP5B	ATP5B	7302	0.0051	0.35	NO
90	ATP5F1	ATP5F1	ATP5F1	7449	0.0033	0.34	NO
91	PPID	PPID	PPID	7847	-0.0011	0.32	NO
92	CASP9	CASP9	CASP9	8262	-0.0055	0.3	NO
93	UBE2G1	UBE2G1	UBE2G1	9158	-0.015	0.25	NO
94	UCHL1	UCHL1	UCHL1	9388	-0.017	0.24	NO
95	UBE2J1	UBE2J1	UBE2J1	9568	-0.02	0.24	NO
96	SLC25A6	SLC25A6	SLC25A6	10336	-0.028	0.2	NO
97	SDHD	SDHD	SDHD	10530	-0.03	0.19	NO
98	APAF1	APAF1	APAF1	10669	-0.032	0.19	NO
99	UQCRC2	UQCRC2	UQCRC2	10884	-0.034	0.18	NO
100	NDUFS1	NDUFS1	NDUFS1	10990	-0.035	0.18	NO
101	CASP3	CASP3	CASP3	11348	-0.04	0.16	NO
102	UBA7	UBA7	UBA7	12178	-0.05	0.13	NO
103	SLC25A5	SLC25A5	SLC25A5	12315	-0.052	0.13	NO
104	UBE2L6	UBE2L6	UBE2L6	12475	-0.055	0.12	NO
105	PARK2	PARK2	PARK2	13401	-0.07	0.083	NO
106	LRRK2	LRRK2	LRRK2	15706	-0.14	-0.026	NO
107	SLC18A2	SLC18A2	SLC18A2	16853	-0.2	-0.062	NO
108	COX6B2	COX6B2	COX6B2	17228	-0.24	-0.051	NO
109	SNCAIP	SNCAIP	SNCAIP	17923	-0.36	-0.04	NO
110	SLC18A1	SLC18A1	SLC18A1	18098	-0.44	0.0087	NO

Figure S31. Get High-res Image This plot shows mRNAseq_cNMF expression data heatmap (on the left) a RunningEnrichmentScore(RES) plot (on the top right) and a Signal2Noise(S2N) plot (on the bottom right) of genes in the pathway: KEGG GLYCINE SERINE AND THREONINE METABOLISM.

Figure S32. Get High-res Image For the top 5 core enriched genes in the pathway: KEGG GLYCINE SERINE AND THREONINE METABOLISM, this volcano plot shows how much they are up/down-regulated and significant. The significance was calculated by empirical bayesian fit

genes ES table in pathway: KEGG VALINE LEUCINE AND ISOLEUCINE DEGRADATION

Table S17. Get Full Table This table shows a Running Enrichment Score (RES) of each gene in this pathway, that is, the enrichment score at this point in the ranked list of genes. All genes are ranked by Signal-to-Noise (S2N), a measure of similarity as default and are used to obtain ES matrix of all genes. In this way, GSEA tool uses expression pattern of not only overlapped genes but also not-overlapped genes to produce ES matrix.

Rank	GENE	SYMBOL	DESC	LIST.LOC	S2N	RES	CORE_ENRICHMENT
1	COX6A2	COX6A2	COX6A2	292	0.28	0.019	YES
2	COX4I2	COX4I2	COX4I2	366	0.25	0.046	YES
3	NDUFA4L2	NDUFA4L2	NDUFA4L2	1067	0.15	0.027	YES
4	COX17	COX17	COX17	1134	0.14	0.041	YES
5	NDUFA3	NDUFA3	NDUFA3	1471	0.12	0.038	YES
6	ATP6V1G2	ATP6V1G2	ATP6V1G2	1498	0.12	0.051	YES
7	ATP6V0E2	ATP6V0E2	ATP6V0E2	1539	0.12	0.064	YES
8	TCIRG1	TCIRG1	TCIRG1	1617	0.11	0.074	YES
9	ATP5I	ATP5I	ATP5I	1655	0.11	0.086	YES
10	COX6C	COX6C	COX6C	1749	0.11	0.094	YES
11	NDUFS8	NDUFS8	NDUFS8	1827	0.1	0.1	YES
12	ATP6V1E2	ATP6V1E2	ATP6V1E2	1842	0.1	0.12	YES
13	ATP5J2	ATP5J2	ATP5J2	1872	0.1	0.13	YES
14	NDUFB1	NDUFB1	NDUFB1	1891	0.1	0.14	YES
15	COX6A1	COX6A1	COX6A1	1936	0.1	0.15	YES
16	NDUFB9	NDUFB9	NDUFB9	1949	0.1	0.16	YES
17	UQCR11	UQCR11	UQCR11	1952	0.1	0.17	YES
18	NDUFB7	NDUFB7	NDUFB7	1970	0.099	0.18	YES
19	NDUFA2	NDUFA2	NDUFA2	1995	0.098	0.19	YES
20	COX5B	COX5B	COX5B	2015	0.098	0.21	YES
21	ATP5D	ATP5D	ATP5D	2280	0.088	0.2	YES
22	ATP6V1C2	ATP6V1C2	ATP6V1C2	2286	0.088	0.21	YES
23	NDUFA7	NDUFA7	NDUFA7	2326	0.086	0.22	YES
24	NDUFC2	NDUFC2	NDUFC2	2374	0.085	0.23	YES
25	UQCR10	UQCR10	UQCR10	2381	0.085	0.24	YES
26	COX7B	COX7B	COX7B	2412	0.084	0.25	YES
27	ATP6V0B	ATP6V0B	ATP6V0B	2413	0.084	0.26	YES
28	COX8C	COX8C	COX8C	2507	0.081	0.26	YES
29	UQCRB	UQCRB	UQCRB	2516	0.08	0.27	YES
30	ATP6V1F	ATP6V1F	ATP6V1F	2536	0.08	0.28	YES
31	NDUFA1	NDUFA1	NDUFA1	2572	0.079	0.29	YES
32	COX7A1	COX7A1	COX7A1	2625	0.078	0.3	YES
33	COX8A	COX8A	COX8A	2687	0.076	0.3	YES
34	NDUFB10	NDUFB10	NDUFB10	2698	0.076	0.31	YES
35	UQCRQ	UQCRQ	UQCRQ	2736	0.075	0.32	YES
36	ATP5E	ATP5E	ATP5E	2845	0.072	0.32	YES
37	NDUFB8	NDUFB8	NDUFB8	2878	0.071	0.33	YES
38	NDUFV3	NDUFV3	NDUFV3	2904	0.071	0.34	YES
39	NDUFB3	NDUFB3	NDUFB3	2923	0.07	0.34	YES
40	NDUFV2	NDUFV2	NDUFV2	2930	0.07	0.35	YES
41	ATP5G1	ATP5G1	ATP5G1	2959	0.069	0.36	YES
42	COX6B1	COX6B1	COX6B1	2997	0.068	0.37	YES
43	NDUFS6	NDUFS6	NDUFS6	3015	0.068	0.38	YES
44	NDUFB6	NDUFB6	NDUFB6	3053	0.067	0.38	YES
45	NDUFS7	NDUFS7	NDUFS7	3217	0.063	0.38	YES
46	NDUFA11	NDUFA11	NDUFA11	3392	0.06	0.38	YES
47	NDUFV1	NDUFV1	NDUFV1	3399	0.059	0.38	YES
48	ATP6V0C	ATP6V0C	ATP6V0C	3411	0.059	0.39	YES
49	NDUFA8	NDUFA8	NDUFA8	3475	0.058	0.4	YES
50	ATP6V1H	ATP6V1H	ATP6V1H	3550	0.056	0.4	YES
51	COX4I1	COX4I1	COX4I1	3566	0.056	0.4	YES
52	COX5A	COX5A	COX5A	3655	0.054	0.41	YES
53	NDUFB2	NDUFB2	NDUFB2	3664	0.054	0.41	YES
54	UQCRHL	UQCRHL	UQCRHL	3675	0.054	0.42	YES
55	ATP6V1C1	ATP6V1C1	ATP6V1C1	3693	0.054	0.42	YES
56	NDUFC1	NDUFC1	NDUFC1	3937	0.049	0.42	YES
57	NDUFAB1	NDUFAB1	NDUFAB1	4062	0.047	0.42	YES
58	ATP6V0A1	ATP6V0A1	ATP6V0A1	4105	0.046	0.42	YES
59	LHPP	LHPP	LHPP	4187	0.045	0.42	YES
60	UQCRH	UQCRH	UQCRH	4294	0.043	0.42	YES
61	COX7A2	COX7A2	COX7A2	4400	0.041	0.42	YES
62	NDUFA9	NDUFA9	NDUFA9	4511	0.039	0.42	YES
63	ATP6V1D	ATP6V1D	ATP6V1D	4543	0.039	0.42	YES
64	ATP5L	ATP5L	ATP5L	4637	0.038	0.42	YES
65	PPA2	PPA2	PPA2	4670	0.037	0.42	YES
66	NDUFA6	NDUFA6	NDUFA6	4683	0.037	0.43	YES
67	ATP5O	ATP5O	ATP5O	4853	0.035	0.42	YES
68	ATP5J	ATP5J	ATP5J	4858	0.035	0.43	YES
69	NDUFA5	NDUFA5	NDUFA5	4881	0.034	0.43	YES
70	NDUFS5	NDUFS5	NDUFS5	4895	0.034	0.43	YES
71	ATP6V0A2	ATP6V0A2	ATP6V0A2	4910	0.034	0.44	YES
72	COX7C	COX7C	COX7C	4976	0.033	0.44	YES
73	NDUFA10	NDUFA10	NDUFA10	5048	0.032	0.44	YES
74	CYC1	CYC1	CYC1	5076	0.032	0.44	YES
75	UQCRC1	UQCRC1	UQCRC1	5089	0.032	0.44	YES
76	COX15	COX15	COX15	5181	0.03	0.44	YES
77	ATP5H	ATP5H	ATP5H	5197	0.03	0.45	YES
78	NDUFA4	NDUFA4	NDUFA4	5212	0.03	0.45	YES
79	NDUFS3	NDUFS3	NDUFS3	5422	0.027	0.44	NO
80	ATP6V1E1	ATP6V1E1	ATP6V1E1	5492	0.026	0.44	NO
81	NDUFB4	NDUFB4	NDUFB4	5558	0.026	0.44	NO
82	ATP5C1	ATP5C1	ATP5C1	5570	0.025	0.44	NO
83	COX7A2L	COX7A2L	COX7A2L	5918	0.021	0.43	NO
84	ATP6V0E1	ATP6V0E1	ATP6V0E1	6045	0.019	0.42	NO
85	ATP6V0D1	ATP6V0D1	ATP6V0D1	6092	0.019	0.42	NO
86	ATP5G2	ATP5G2	ATP5G2	6100	0.019	0.42	NO
87	SDHB	SDHB	SDHB	6356	0.016	0.41	NO
88	NDUFB5	NDUFB5	NDUFB5	6438	0.015	0.41	NO
89	ATP6AP1	ATP6AP1	ATP6AP1	6448	0.015	0.41	NO
90	SDHA	SDHA	SDHA	6455	0.015	0.41	NO
91	UQCRFS1	UQCRFS1	UQCRFS1	6707	0.012	0.4	NO
92	NDUFS4	NDUFS4	NDUFS4	6821	0.011	0.39	NO
93	NDUFS2	NDUFS2	NDUFS2	6910	0.0094	0.39	NO
94	ATP5G3	ATP5G3	ATP5G3	6990	0.0085	0.39	NO
95	ATP5A1	ATP5A1	ATP5A1	7015	0.0083	0.39	NO
96	SDHC	SDHC	SDHC	7055	0.0078	0.39	NO
97	ATP5B	ATP5B	ATP5B	7302	0.0051	0.37	NO
98	PPA1	PPA1	PPA1	7329	0.0047	0.37	NO
99	ATP5F1	ATP5F1	ATP5F1	7449	0.0033	0.37	NO
100	COX10	COX10	COX10	7695	0.00077	0.35	NO
101	ATP6V1B2	ATP6V1B2	ATP6V1B2	8008	-0.0029	0.34	NO
102	ATP6V1G1	ATP6V1G1	ATP6V1G1	8642	-0.0096	0.3	NO
103	ATP6V1A	ATP6V1A	ATP6V1A	9866	-0.023	0.24	NO
104	COX11	COX11	COX11	9897	-0.023	0.24	NO
105	SDHD	SDHD	SDHD	10530	-0.03	0.21	NO
106	UQCRC2	UQCRC2	UQCRC2	10884	-0.034	0.19	NO
107	NDUFS1	NDUFS1	NDUFS1	10990	-0.035	0.19	NO
108	ATP4B	ATP4B	ATP4B	12262	-0.052	0.13	NO
109	ATP6V0D2	ATP6V0D2	ATP6V0D2	15907	-0.14	-0.056	NO
110	ATP6V1G3	ATP6V1G3	ATP6V1G3	17030	-0.22	-0.09	NO
111	COX6B2	COX6B2	COX6B2	17228	-0.24	-0.072	NO
112	ATP6V1B1	ATP6V1B1	ATP6V1B1	17243	-0.24	-0.042	NO
113	ATP6V0A4	ATP6V0A4	ATP6V0A4	17459	-0.27	-0.021	NO
114	ATP12A	ATP12A	ATP12A	18183	-0.52	0.004	NO

Figure S33. Get High-res Image This plot shows mRNAseq_cNMF expression data heatmap (on the left) a RunningEnrichmentScore(RES) plot (on the top right) and a Signal2Noise(S2N) plot (on the bottom right) of genes in the pathway: KEGG VALINE LEUCINE AND ISOLEUCINE DEGRADATION.

Figure S34. Get High-res Image For the top 5 core enriched genes in the pathway: KEGG VALINE LEUCINE AND ISOLEUCINE DEGRADATION, this volcano plot shows how much they are up/down-regulated and significant. The significance was calculated by empirical bayesian fit

genes ES table in pathway: KEGG TYROSINE METABOLISM

Table S18. Get Full Table This table shows a Running Enrichment Score (RES) of each gene in this pathway, that is, the enrichment score at this point in the ranked list of genes. All genes are ranked by Signal-to-Noise (S2N), a measure of similarity as default and are used to obtain ES matrix of all genes. In this way, GSEA tool uses expression pattern of not only overlapped genes but also not-overlapped genes to produce ES matrix.

Rank	GENE	SYMBOL	DESC	LIST.LOC	S2N	RES	CORE_ENRICHMENT
1	GNMT	GNMT	GNMT	30	0.48	0.16	YES
2	GAMT	GAMT	GAMT	543	0.21	0.2	YES
3	CBS	CBS	CBS	545	0.21	0.27	YES
4	AOC2	AOC2	AOC2	593	0.21	0.33	YES
5	SDS	SDS	SDS	939	0.16	0.37	YES
6	PSAT1	PSAT1	PSAT1	959	0.16	0.42	YES
7	CHDH	CHDH	CHDH	1324	0.13	0.44	YES
8	MAOA	MAOA	MAOA	1993	0.098	0.44	YES
9	SARDH	SARDH	SARDH	2156	0.092	0.46	YES
10	DMGDH	DMGDH	DMGDH	2448	0.083	0.47	YES
11	GCAT	GCAT	GCAT	2758	0.075	0.48	YES
12	ALAS2	ALAS2	ALAS2	2811	0.073	0.5	YES
13	PSPH	PSPH	PSPH	4263	0.043	0.44	NO
14	CTH	CTH	CTH	5495	0.026	0.38	NO
15	ALAS1	ALAS1	ALAS1	5823	0.022	0.36	NO
16	SRR	SRR	SRR	5980	0.02	0.36	NO
17	DLD	DLD	DLD	6677	0.012	0.33	NO
18	BHMT	BHMT	BHMT	6881	0.0098	0.32	NO
19	SHMT2	SHMT2	SHMT2	7727	0.00029	0.28	NO
20	GLYCTK	GLYCTK	GLYCTK	7909	-0.0018	0.26	NO
21	MAOB	MAOB	MAOB	8371	-0.0066	0.24	NO
22	PHGDH	PHGDH	PHGDH	8870	-0.012	0.22	NO
23	SHMT1	SHMT1	SHMT1	11001	-0.035	0.11	NO
24	AGXT	AGXT	AGXT	13549	-0.072	-0.0022	NO
25	AOC3	AOC3	AOC3	14138	-0.085	-0.0064	NO
26	GATM	GATM	GATM	15458	-0.13	-0.037	NO
27	PIPOX	PIPOX	PIPOX	15777	-0.14	-0.0094	NO
28	GLDC	GLDC	GLDC	18104	-0.44	0.0083	NO

Figure S35. Get High-res Image This plot shows mRNAseq_cNMF expression data heatmap (on the left) a RunningEnrichmentScore(RES) plot (on the top right) and a Signal2Noise(S2N) plot (on the bottom right) of genes in the pathway: KEGG TYROSINE METABOLISM.

Figure S36. Get High-res Image For the top 5 core enriched genes in the pathway: KEGG TYROSINE METABOLISM, this volcano plot shows how much they are up/down-regulated and significant. The significance was calculated by empirical bayesian fit

genes ES table in pathway: KEGG GLUTATHIONE METABOLISM

Table S19. Get Full Table This table shows a Running Enrichment Score (RES) of each gene in this pathway, that is, the enrichment score at this point in the ranked list of genes. All genes are ranked by Signal-to-Noise (S2N), a measure of similarity as default and are used to obtain ES matrix of all genes. In this way, GSEA tool uses expression pattern of not only overlapped genes but also not-overlapped genes to produce ES matrix.

Rank	GENE	SYMBOL	DESC	LIST.LOC	S2N	RES	CORE_ENRICHMENT
1	SHFM1	SHFM1	SHFM1	1680	0.11	0.0052	YES
2	PSMC1	PSMC1	PSMC1	3194	0.064	-0.021	YES
3	PSMB6	PSMB6	PSMB6	3410	0.059	0.019	YES
4	PSME2	PSME2	PSME2	3616	0.055	0.057	YES
5	PSMB7	PSMB7	PSMB7	3718	0.053	0.098	YES
6	PSMA4	PSMA4	PSMA4	3835	0.051	0.14	YES
7	PSMB3	PSMB3	PSMB3	3837	0.051	0.18	YES
8	PSMB11	PSMB11	PSMB11	4121	0.046	0.21	YES
9	POMP	POMP	POMP	4315	0.042	0.23	YES
10	PSMB5	PSMB5	PSMB5	4736	0.036	0.24	YES
11	PSMC2	PSMC2	PSMC2	4789	0.036	0.27	YES
12	PSMA2	PSMA2	PSMA2	5070	0.032	0.28	YES
13	PSMB4	PSMB4	PSMB4	5149	0.03	0.31	YES
14	PSMA3	PSMA3	PSMA3	5173	0.03	0.33	YES
15	PSMC3	PSMC3	PSMC3	5268	0.029	0.35	YES
16	PSMD4	PSMD4	PSMD4	5321	0.028	0.38	YES
17	PSMA6	PSMA6	PSMA6	5716	0.024	0.37	YES
18	PSMB2	PSMB2	PSMB2	5854	0.022	0.39	YES
19	PSMD8	PSMD8	PSMD8	5931	0.021	0.4	YES
20	PSMA5	PSMA5	PSMA5	5933	0.021	0.42	YES
21	PSMC5	PSMC5	PSMC5	6000	0.02	0.43	YES
22	PSMA7	PSMA7	PSMA7	6425	0.015	0.42	YES
23	PSMD14	PSMD14	PSMD14	6598	0.013	0.42	YES
24	PSMC6	PSMC6	PSMC6	6637	0.013	0.43	YES
25	PSMB1	PSMB1	PSMB1	7304	0.0051	0.4	NO
26	PSMD11	PSMD11	PSMD11	7315	0.0049	0.4	NO
27	PSMD13	PSMD13	PSMD13	7362	0.0044	0.41	NO
28	PSME1	PSME1	PSME1	7552	0.0024	0.4	NO
29	PSMC4	PSMC4	PSMC4	7623	0.0017	0.4	NO
30	PSMD7	PSMD7	PSMD7	7648	0.0013	0.4	NO
31	PSMD3	PSMD3	PSMD3	7666	0.0011	0.4	NO
32	PSMD1	PSMD1	PSMD1	7747	0.000038	0.39	NO
33	PSME3	PSME3	PSME3	8028	-0.0032	0.38	NO
34	PSMD6	PSMD6	PSMD6	8078	-0.0037	0.38	NO
35	PSMD12	PSMD12	PSMD12	8088	-0.0038	0.38	NO
36	PSME4	PSME4	PSME4	8461	-0.0076	0.37	NO
37	PSMA1	PSMA1	PSMA1	8560	-0.0086	0.37	NO
38	PSMF1	PSMF1	PSMF1	8581	-0.0088	0.38	NO
39	PSMD2	PSMD2	PSMD2	8624	-0.0094	0.38	NO
40	IFNG	IFNG	IFNG	10546	-0.03	0.3	NO
41	PSMB9	PSMB9	PSMB9	12471	-0.055	0.25	NO
42	PSMB8	PSMB8	PSMB8	13909	-0.08	0.24	NO

Figure S37. Get High-res Image This plot shows mRNAseq_cNMF expression data heatmap (on the left) a RunningEnrichmentScore(RES) plot (on the top right) and a Signal2Noise(S2N) plot (on the bottom right) of genes in the pathway: KEGG GLUTATHIONE METABOLISM.

Figure S38. Get High-res Image For the top 5 core enriched genes in the pathway: KEGG GLUTATHIONE METABOLISM, this volcano plot shows how much they are up/down-regulated and significant. The significance was calculated by empirical bayesian fit

genes ES table in pathway: KEGG AMINO SUGAR AND NUCLEOTIDE SUGAR METABOLISM

Table S20. Get Full Table This table shows a Running Enrichment Score (RES) of each gene in this pathway, that is, the enrichment score at this point in the ranked list of genes. All genes are ranked by Signal-to-Noise (S2N), a measure of similarity as default and are used to obtain ES matrix of all genes. In this way, GSEA tool uses expression pattern of not only overlapped genes but also not-overlapped genes to produce ES matrix.

Rank	GENE	SYMBOL	DESC	LIST.LOC	S2N	RES	CORE_ENRICHMENT
1	RPL3L	RPL3L	RPL3L	102	0.37	0.13	YES
2	RPL22L1	RPL22L1	RPL22L1	1557	0.12	0.088	YES
3	RPL36A	RPL36A	RPL36A	2452	0.083	0.068	YES
4	RPL9	RPL9	RPL9	2456	0.083	0.097	YES
5	RPS27L	RPS27L	RPS27L	2721	0.075	0.11	YES
6	RPS20	RPS20	RPS20	3051	0.067	0.12	YES
7	MRPL13	MRPL13	MRPL13	3242	0.063	0.13	YES
8	RPS10	RPS10	RPS10	3788	0.052	0.12	YES
9	RPS15	RPS15	RPS15	3818	0.051	0.13	YES
10	RPL28	RPL28	RPL28	3933	0.049	0.14	YES
11	RPL26	RPL26	RPL26	4097	0.046	0.15	YES
12	RPL13	RPL13	RPL13	4161	0.045	0.16	YES
13	RPL39	RPL39	RPL39	4274	0.043	0.17	YES
14	RPL36AL	RPL36AL	RPL36AL	4288	0.043	0.19	YES
15	RPL12	RPL12	RPL12	4290	0.043	0.2	YES
16	RPL35	RPL35	RPL35	4428	0.041	0.21	YES
17	RPL37A	RPL37A	RPL37A	4451	0.04	0.22	YES
18	RPLP2	RPLP2	RPLP2	4461	0.04	0.24	YES
19	RPL26L1	RPL26L1	RPL26L1	4482	0.04	0.25	YES
20	RPL32	RPL32	RPL32	4570	0.038	0.26	YES
21	FAU	FAU	FAU	4601	0.038	0.27	YES
22	RPS26	RPS26	RPS26	4606	0.038	0.28	YES
23	RPS19	RPS19	RPS19	4631	0.038	0.29	YES
24	RPS21	RPS21	RPS21	4634	0.038	0.31	YES
25	RPL23	RPL23	RPL23	4641	0.038	0.32	YES
26	RPL38	RPL38	RPL38	4654	0.037	0.33	YES
27	RPL14	RPL14	RPL14	4717	0.036	0.34	YES
28	RPL30	RPL30	RPL30	4768	0.036	0.35	YES
29	RPL8	RPL8	RPL8	4901	0.034	0.36	YES
30	RPL36	RPL36	RPL36	4906	0.034	0.37	YES
31	UBA52	UBA52	UBA52	4919	0.034	0.38	YES
32	RPL37	RPL37	RPL37	4992	0.033	0.39	YES
33	RPS16	RPS16	RPS16	5219	0.03	0.38	YES
34	RPL27	RPL27	RPL27	5244	0.029	0.4	YES
35	RPSA	RPSA	RPSA	5311	0.028	0.4	YES
36	RPS24	RPS24	RPS24	5318	0.028	0.41	YES
37	RPL35A	RPL35A	RPL35A	5331	0.028	0.42	YES
38	RPS25	RPS25	RPS25	5365	0.028	0.43	YES
39	RPL24	RPL24	RPL24	5395	0.027	0.44	YES
40	RPL23A	RPL23A	RPL23A	5453	0.027	0.44	YES
41	RPL29	RPL29	RPL29	5463	0.027	0.45	YES
42	RPLP1	RPLP1	RPLP1	5480	0.026	0.46	YES
43	RPS6	RPS6	RPS6	5502	0.026	0.47	YES
44	RPL19	RPL19	RPL19	5596	0.025	0.47	YES
45	RPS9	RPS9	RPS9	5657	0.024	0.48	YES
46	RPS5	RPS5	RPS5	5686	0.024	0.48	YES
47	RPL31	RPL31	RPL31	5722	0.023	0.49	YES
48	RPS8	RPS8	RPS8	5753	0.023	0.5	YES
49	RPL34	RPL34	RPL34	5775	0.022	0.5	YES
50	RPS29	RPS29	RPS29	6015	0.02	0.5	YES
51	RPL18A	RPL18A	RPL18A	6137	0.018	0.5	YES
52	RPS27A	RPS27A	RPS27A	6161	0.018	0.5	YES
53	RPL27A	RPL27A	RPL27A	6322	0.016	0.5	YES
54	RPL15	RPL15	RPL15	6327	0.016	0.5	YES
55	RPLP0	RPLP0	RPLP0	6382	0.015	0.51	YES
56	RPS2	RPS2	RPS2	6454	0.015	0.51	YES
57	RPS13	RPS13	RPS13	6469	0.014	0.51	YES
58	RPL41	RPL41	RPL41	6523	0.014	0.52	YES
59	RPS11	RPS11	RPS11	6526	0.014	0.52	YES
60	RPL7A	RPL7A	RPL7A	6528	0.014	0.52	YES
61	RPS23	RPS23	RPS23	6586	0.013	0.53	YES
62	RPL13A	RPL13A	RPL13A	6687	0.012	0.52	NO
63	RPL7	RPL7	RPL7	6830	0.01	0.52	NO
64	RPS18	RPS18	RPS18	6880	0.0098	0.52	NO
65	RPS4X	RPS4X	RPS4X	6955	0.0089	0.52	NO
66	RPS17	RPS17	RPS17	7022	0.0082	0.52	NO
67	RPL4	RPL4	RPL4	7032	0.008	0.52	NO
68	RPL3	RPL3	RPL3	7086	0.0074	0.52	NO
69	RPL10	RPL10	RPL10	7306	0.0051	0.51	NO
70	RPS4Y1	RPS4Y1	RPS4Y1	7324	0.0049	0.51	NO
71	RPS7	RPS7	RPS7	7403	0.0038	0.51	NO
72	RPS12	RPS12	RPS12	7539	0.0025	0.5	NO
73	RPL11	RPL11	RPL11	7662	0.0011	0.5	NO
74	RSL24D1	RSL24D1	RSL24D1	7797	-0.00054	0.49	NO
75	RPL10A	RPL10A	RPL10A	7850	-0.0011	0.49	NO
76	RPL17	RPL17	RPL17	8038	-0.0033	0.48	NO
77	RPS3	RPS3	RPS3	8104	-0.0039	0.48	NO
78	RPL6	RPL6	RPL6	8162	-0.0046	0.47	NO
79	RPS15A	RPS15A	RPS15A	8317	-0.0061	0.47	NO
80	RPL5	RPL5	RPL5	8881	-0.012	0.44	NO
81	RPS3A	RPS3A	RPS3A	9403	-0.017	0.42	NO
82	RPL22	RPL22	RPL22	9442	-0.018	0.42	NO
83	RPS28	RPS28	RPS28	10798	-0.033	0.36	NO
84	RPS27	RPS27	RPS27	13076	-0.064	0.26	NO
85	RPL21	RPL21	RPL21	13807	-0.078	0.24	NO

Figure S39. Get High-res Image This plot shows mRNAseq_cNMF expression data heatmap (on the left) a RunningEnrichmentScore(RES) plot (on the top right) and a Signal2Noise(S2N) plot (on the bottom right) of genes in the pathway: KEGG AMINO SUGAR AND NUCLEOTIDE SUGAR METABOLISM.

Figure S40. Get High-res Image For the top 5 core enriched genes in the pathway: KEGG AMINO SUGAR AND NUCLEOTIDE SUGAR METABOLISM, this volcano plot shows how much they are up/down-regulated and significant. The significance was calculated by empirical bayesian fit

Fold change

For the top enriched genes, if you want to check whether they are

up-regulated, please check the list of up-regulated genes
down-regulated, please check the list of down-regulated genes

Expression level

For the top enriched genes, if you want to check whether they are

highly expressed genes, please check the list of high (top 30%) expressed genes
low expressed genes, please check the list of low (bottom 30%) expressed genes

An expression pattern of top(30%)/middle(30%)/low(30%) in this subtype against other subtypes is available in a heatmap

Significant gene list

For the top enriched genes, if you want to check whether they are

significantly differently expressed genes by eBayes lm fit, please check the list of significant genes

Subtype clus3 enriched pathways

Table 5. Get Full Table This table shows top 10 pathways which are significantly enriched in cluster clus3. It displays only significant gene sets satisfying nom.p.val.threshold (-1), fwer.p.val.threshold (-1) , fdr.q.val.threshold (0.25) and the default table is sorted by Normalized Enrichment Score (NES). Further details on NES statistics, please visit The Broad GSEA website.

GeneSet(GS)	Size(#genes)	genes.ES.table	ES	NES	NOM.p.val	FDR.q.val	FWER.p.val	Tag..	Gene..	Signal	FDR..median.	glob.p.val
BIOCARTA CARM ER PATHWAY	34	genes.ES.table	0.29	1	0.42	0.91	1	0.41	0.28	0.3	0.85	0.33
BIOCARTA HIVNEF PATHWAY	57	genes.ES.table	0.24	0.96	0.51	0.91	1	0.39	0.27	0.28	0.86	0.33
BIOCARTA MPR PATHWAY	31	genes.ES.table	0.34	1.1	0.3	0.99	1	0.19	0.12	0.17	0.89	0.39
BIOCARTA TNFR1 PATHWAY	28	genes.ES.table	0.36	1.2	0.29	0.92	1	0.39	0.21	0.31	0.82	0.34
KEGG CITRATE CYCLE TCA CYCLE	29	genes.ES.table	0.49	1.6	0.059	0.19	0.68	0.034	0.00077	0.034	0.11	0.017
KEGG PENTOSE PHOSPHATE PATHWAY	25	genes.ES.table	0.35	1.1	0.34	0.87	1	0.32	0.17	0.27	0.78	0.29
KEGG N GLYCAN BIOSYNTHESIS	45	genes.ES.table	0.47	1.6	0.051	0.25	0.67	0.4	0.26	0.3	0.14	0.048
KEGG AMINOACYL TRNA BIOSYNTHESIS	40	genes.ES.table	0.51	1.7	0.042	0.28	0.37	0.62	0.36	0.4	0	0.081
KEGG RIBOSOME	85	genes.ES.table	0.39	0.92	0.55	0.86	1	0.86	0.42	0.5	0.82	0.26
KEGG RNA DEGRADATION	56	genes.ES.table	0.33	1.6	0.053	0.33	0.64	0.54	0.36	0.35	0.18	0.081

genes ES table in pathway: BIOCARTA CARM ER PATHWAY

Table S21. Get Full Table This table shows a Running Enrichment Score (RES) of each gene in this pathway, that is, the enrichment score at this point in the ranked list of genes. All genes are ranked by Signal-to-Noise (S2N), a measure of similarity as default and are used to obtain ES matrix of all genes. In this way, GSEA tool uses expression pattern of not only overlapped genes but also not-overlapped genes to produce ES matrix.

Rank	GENE	SYMBOL	DESC	LIST.LOC	S2N	RES	CORE_ENRICHMENT
1	DARS2	DARS2	DARS2	1732	0.1	-0.015	YES
2	NARS2	NARS2	NARS2	1892	0.096	0.052	YES
3	EPRS	EPRS	EPRS	2208	0.084	0.1	YES
4	RARS2	RARS2	RARS2	2502	0.074	0.14	YES
5	VARS	VARS	VARS	2986	0.064	0.17	YES
6	IARS	IARS	IARS	3722	0.051	0.17	YES
7	FARSB	FARSB	FARSB	3899	0.048	0.2	YES
8	PARS2	PARS2	PARS2	4033	0.046	0.22	YES
9	RARS	RARS	RARS	4301	0.043	0.24	YES
10	LARS	LARS	LARS	4314	0.043	0.28	YES
11	IARS2	IARS2	IARS2	4445	0.041	0.3	YES
12	VARS2	VARS2	VARS2	4532	0.04	0.33	YES
13	YARS2	YARS2	YARS2	4535	0.04	0.36	YES
14	SEPSECS	SEPSECS	SEPSECS	4602	0.039	0.39	YES
15	EARS2	EARS2	EARS2	4651	0.039	0.41	YES
16	QARS	QARS	QARS	5183	0.032	0.41	YES
17	MARS2	MARS2	MARS2	5184	0.032	0.44	YES
18	WARS2	WARS2	WARS2	5273	0.031	0.46	YES
19	YARS	YARS	YARS	5536	0.028	0.46	YES
20	TARSL2	TARSL2	TARSL2	5546	0.028	0.48	YES
21	LARS2	LARS2	LARS2	5657	0.027	0.5	YES
22	GARS	GARS	GARS	6129	0.022	0.49	YES
23	TARS	TARS	TARS	6233	0.021	0.5	YES
24	CARS2	CARS2	CARS2	6524	0.018	0.5	YES
25	DARS	DARS	DARS	6637	0.017	0.51	YES
26	NARS	NARS	NARS	7053	0.013	0.5	NO
27	FARSA	FARSA	FARSA	7095	0.013	0.5	NO
28	HARS2	HARS2	HARS2	7279	0.011	0.5	NO
29	WARS	WARS	WARS	7770	0.0063	0.48	NO
30	MARS	MARS	MARS	7821	0.0058	0.48	NO
31	AARS2	AARS2	AARS2	7919	0.0049	0.48	NO
32	MTFMT	MTFMT	MTFMT	8313	0.00086	0.46	NO
33	SARS2	SARS2	SARS2	8479	-0.0008	0.45	NO
34	SARS	SARS	SARS	8512	-0.0011	0.45	NO
35	CARS	CARS	CARS	8587	-0.0018	0.45	NO
36	AARS	AARS	AARS	8893	-0.0049	0.44	NO
37	PSTK	PSTK	PSTK	9022	-0.0062	0.43	NO
38	KARS	KARS	KARS	9511	-0.012	0.42	NO
39	HARS	HARS	HARS	10632	-0.026	0.38	NO
40	FARS2	FARS2	FARS2	12319	-0.054	0.33	NO

Figure S41. Get High-res Image This plot shows mRNAseq_cNMF expression data heatmap (on the left) a RunningEnrichmentScore(RES) plot (on the top right) and a Signal2Noise(S2N) plot (on the bottom right) of genes in the pathway: BIOCARTA CARM ER PATHWAY.

Figure S42. Get High-res Image For the top 5 core enriched genes in the pathway: BIOCARTA CARM ER PATHWAY, this volcano plot shows how much they are up/down-regulated and significant. The significance was calculated by empirical bayesian fit

genes ES table in pathway: BIOCARTA HIVNEF PATHWAY

Table S22. Get Full Table This table shows a Running Enrichment Score (RES) of each gene in this pathway, that is, the enrichment score at this point in the ranked list of genes. All genes are ranked by Signal-to-Noise (S2N), a measure of similarity as default and are used to obtain ES matrix of all genes. In this way, GSEA tool uses expression pattern of not only overlapped genes but also not-overlapped genes to produce ES matrix.

Rank	GENE	SYMBOL	DESC	LIST.LOC	S2N	RES	CORE_ENRICHMENT
1	RQCD1	RQCD1	RQCD1	1823	0.098	-0.046	YES
2	CNOT6	CNOT6	CNOT6	2145	0.086	-0.015	YES
3	DCPS	DCPS	DCPS	3069	0.062	-0.032	YES
4	ZCCHC7	ZCCHC7	ZCCHC7	3272	0.058	-0.01	YES
5	XRN2	XRN2	XRN2	3367	0.057	0.016	YES
6	HSPD1	HSPD1	HSPD1	3576	0.053	0.034	YES
7	TTC37	TTC37	TTC37	3592	0.053	0.063	YES
8	ENO1	ENO1	ENO1	3782	0.05	0.08	YES
9	PATL1	PATL1	PATL1	3887	0.048	0.1	YES
10	CNOT10	CNOT10	CNOT10	4106	0.045	0.11	YES
11	DCP2	DCP2	DCP2	4298	0.043	0.13	YES
12	EDC3	EDC3	EDC3	4338	0.042	0.15	YES
13	DCP1A	DCP1A	DCP1A	4400	0.042	0.17	YES
14	EXOSC3	EXOSC3	EXOSC3	4508	0.04	0.18	YES
15	HSPA9	HSPA9	HSPA9	4658	0.039	0.2	YES
16	EXOSC10	EXOSC10	EXOSC10	4708	0.038	0.22	YES
17	PAPOLG	PAPOLG	PAPOLG	4837	0.036	0.23	YES
18	EXOSC4	EXOSC4	EXOSC4	4916	0.036	0.25	YES
19	CNOT1	CNOT1	CNOT1	5146	0.033	0.25	YES
20	CNOT2	CNOT2	CNOT2	5271	0.031	0.26	YES
21	CNOT3	CNOT3	CNOT3	5331	0.031	0.28	YES
22	DDX6	DDX6	DDX6	5337	0.03	0.29	YES
23	LSM2	LSM2	LSM2	5504	0.029	0.3	YES
24	PARN	PARN	PARN	5808	0.026	0.3	YES
25	EXOSC9	EXOSC9	EXOSC9	6051	0.023	0.3	YES
26	NAA38	NAA38	NAA38	6100	0.023	0.31	YES
27	PAPOLA	PAPOLA	PAPOLA	6135	0.022	0.32	YES
28	EXOSC2	EXOSC2	EXOSC2	6292	0.021	0.32	YES
29	PAPOLB	PAPOLB	PAPOLB	6413	0.019	0.32	YES
30	EXOSC5	EXOSC5	EXOSC5	6511	0.018	0.33	YES
31	DIS3	DIS3	DIS3	6776	0.016	0.32	NO
32	PNPT1	PNPT1	PNPT1	6977	0.014	0.32	NO
33	CNOT6L	CNOT6L	CNOT6L	7411	0.0098	0.3	NO
34	PAPD7	PAPD7	PAPD7	7489	0.009	0.3	NO
35	SKIV2L	SKIV2L	SKIV2L	7724	0.0066	0.29	NO
36	EDC4	EDC4	EDC4	7808	0.0059	0.29	NO
37	DCP1B	DCP1B	DCP1B	7896	0.0052	0.29	NO
38	XRN1	XRN1	XRN1	7911	0.005	0.29	NO
39	LSM7	LSM7	LSM7	8081	0.0033	0.28	NO
40	EXOSC8	EXOSC8	EXOSC8	8203	0.0023	0.28	NO
41	CNOT7	CNOT7	CNOT7	8242	0.0018	0.28	NO
42	LSM4	LSM4	LSM4	8387	0.0001	0.27	NO
43	EXOSC7	EXOSC7	EXOSC7	8435	-0.00039	0.27	NO
44	SKIV2L2	SKIV2L2	SKIV2L2	8820	-0.0043	0.25	NO
45	LSM5	LSM5	LSM5	8854	-0.0045	0.25	NO
46	LSM3	LSM3	LSM3	8965	-0.0057	0.25	NO
47	CNOT4	CNOT4	CNOT4	9520	-0.012	0.22	NO
48	LSM6	LSM6	LSM6	9721	-0.014	0.22	NO
49	WDR61	WDR61	WDR61	10470	-0.024	0.19	NO
50	EXOSC6	EXOSC6	EXOSC6	11109	-0.033	0.18	NO
51	C1D	C1D	C1D	11455	-0.038	0.18	NO
52	MPHOSPH6	MPHOSPH6	MPHOSPH6	11461	-0.038	0.2	NO
53	EXOSC1	EXOSC1	EXOSC1	11722	-0.042	0.21	NO
54	ENO2	ENO2	ENO2	12000	-0.048	0.22	NO
55	LSM1	LSM1	LSM1	14223	-0.11	0.16	NO
56	ENO3	ENO3	ENO3	14608	-0.12	0.2	NO

Figure S43. Get High-res Image This plot shows mRNAseq_cNMF expression data heatmap (on the left) a RunningEnrichmentScore(RES) plot (on the top right) and a Signal2Noise(S2N) plot (on the bottom right) of genes in the pathway: BIOCARTA HIVNEF PATHWAY.

Figure S44. Get High-res Image For the top 5 core enriched genes in the pathway: BIOCARTA HIVNEF PATHWAY, this volcano plot shows how much they are up/down-regulated and significant. The significance was calculated by empirical bayesian fit

genes ES table in pathway: BIOCARTA MPR PATHWAY

Table S23. Get Full Table This table shows a Running Enrichment Score (RES) of each gene in this pathway, that is, the enrichment score at this point in the ranked list of genes. All genes are ranked by Signal-to-Noise (S2N), a measure of similarity as default and are used to obtain ES matrix of all genes. In this way, GSEA tool uses expression pattern of not only overlapped genes but also not-overlapped genes to produce ES matrix.

Rank	GENE	SYMBOL	DESC	LIST.LOC	S2N	RES	CORE_ENRICHMENT
1	MGAT5B	MGAT5B	MGAT5B	10	0.72	0.26	YES
2	ALG11	ALG11	ALG11	491	0.22	0.32	YES
3	MAN2A1	MAN2A1	MAN2A1	913	0.16	0.35	YES
4	MGAT5	MGAT5	MGAT5	1257	0.13	0.38	YES
5	ALG10B	ALG10B	ALG10B	1729	0.1	0.39	YES
6	MGAT4B	MGAT4B	MGAT4B	2569	0.073	0.37	YES
7	MAN2A2	MAN2A2	MAN2A2	3122	0.061	0.36	YES
8	ST6GAL1	ST6GAL1	ST6GAL1	3154	0.061	0.39	YES
9	ALG6	ALG6	ALG6	3287	0.058	0.4	YES
10	MOGS	MOGS	MOGS	3293	0.058	0.42	YES
11	GANAB	GANAB	GANAB	3307	0.058	0.44	YES
12	STT3A	STT3A	STT3A	3663	0.052	0.44	YES
13	ALG10	ALG10	ALG10	3741	0.05	0.45	YES
14	ALG13	ALG13	ALG13	4355	0.042	0.44	YES
15	B4GALT3	B4GALT3	B4GALT3	4484	0.041	0.44	YES
16	DDOST	DDOST	DDOST	4678	0.038	0.45	YES
17	FUT8	FUT8	FUT8	4691	0.038	0.46	YES
18	STT3B	STT3B	STT3B	4707	0.038	0.47	YES
19	MAN1B1	MAN1B1	MAN1B1	5302	0.031	0.45	NO
20	DPAGT1	DPAGT1	DPAGT1	5482	0.029	0.45	NO
21	RPN2	RPN2	RPN2	5700	0.027	0.45	NO
22	B4GALT2	B4GALT2	B4GALT2	6303	0.02	0.43	NO
23	MGAT4A	MGAT4A	MGAT4A	6543	0.018	0.42	NO
24	DOLPP1	DOLPP1	DOLPP1	6947	0.014	0.4	NO
25	DPM1	DPM1	DPM1	6976	0.014	0.41	NO
26	MAN1A2	MAN1A2	MAN1A2	7089	0.013	0.4	NO
27	ALG9	ALG9	ALG9	7720	0.0067	0.37	NO
28	RPN1	RPN1	RPN1	7850	0.0056	0.37	NO
29	ALG2	ALG2	ALG2	8780	-0.0038	0.32	NO
30	MGAT2	MGAT2	MGAT2	9172	-0.0078	0.3	NO
31	MAN1C1	MAN1C1	MAN1C1	9209	-0.0081	0.3	NO
32	ALG14	ALG14	ALG14	9421	-0.011	0.29	NO
33	ALG1	ALG1	ALG1	9991	-0.017	0.27	NO
34	ALG8	ALG8	ALG8	10430	-0.023	0.25	NO
35	DPM3	DPM3	DPM3	10513	-0.024	0.26	NO
36	DAD1	DAD1	DAD1	10815	-0.028	0.25	NO
37	ALG12	ALG12	ALG12	11130	-0.033	0.24	NO
38	ALG3	ALG3	ALG3	11180	-0.034	0.25	NO
39	B4GALT1	B4GALT1	B4GALT1	11417	-0.037	0.26	NO
40	MGAT1	MGAT1	MGAT1	11638	-0.041	0.26	NO
41	MGAT3	MGAT3	MGAT3	11710	-0.042	0.27	NO
42	DPM2	DPM2	DPM2	12359	-0.055	0.25	NO
43	ALG5	ALG5	ALG5	12526	-0.059	0.27	NO
44	TUSC3	TUSC3	TUSC3	12749	-0.063	0.28	NO
45	MAN1A1	MAN1A1	MAN1A1	12930	-0.068	0.29	NO

Figure S45. Get High-res Image This plot shows mRNAseq_cNMF expression data heatmap (on the left) a RunningEnrichmentScore(RES) plot (on the top right) and a Signal2Noise(S2N) plot (on the bottom right) of genes in the pathway: BIOCARTA MPR PATHWAY.

Figure S46. Get High-res Image For the top 5 core enriched genes in the pathway: BIOCARTA MPR PATHWAY, this volcano plot shows how much they are up/down-regulated and significant. The significance was calculated by empirical bayesian fit

genes ES table in pathway: BIOCARTA TNFR1 PATHWAY

Table S24. Get Full Table This table shows a Running Enrichment Score (RES) of each gene in this pathway, that is, the enrichment score at this point in the ranked list of genes. All genes are ranked by Signal-to-Noise (S2N), a measure of similarity as default and are used to obtain ES matrix of all genes. In this way, GSEA tool uses expression pattern of not only overlapped genes but also not-overlapped genes to produce ES matrix.

Rank	GENE	SYMBOL	DESC	LIST.LOC	S2N	RES	CORE_ENRICHMENT
1	OGDHL	OGDHL	OGDHL	14	0.68	0.49	YES
2	DLAT	DLAT	DLAT	2412	0.077	0.41	NO
3	CS	CS	CS	4653	0.039	0.32	NO
4	MDH2	MDH2	MDH2	4943	0.035	0.33	NO
5	PDHA1	PDHA1	PDHA1	5244	0.032	0.33	NO
6	FH	FH	FH	5299	0.031	0.35	NO
7	SUCLG1	SUCLG1	SUCLG1	5820	0.026	0.34	NO
8	SDHB	SDHB	SDHB	6173	0.022	0.34	NO
9	SDHC	SDHC	SDHC	6911	0.015	0.31	NO
10	OGDH	OGDH	OGDH	7483	0.0091	0.28	NO
11	SDHD	SDHD	SDHD	7637	0.0076	0.28	NO
12	DLD	DLD	DLD	7638	0.0076	0.29	NO
13	PDHB	PDHB	PDHB	7665	0.0074	0.29	NO
14	ACO2	ACO2	ACO2	8190	0.0024	0.26	NO
15	PCK2	PCK2	PCK2	8399	-0.000021	0.25	NO
16	ACLY	ACLY	ACLY	8455	-0.00051	0.25	NO
17	SDHA	SDHA	SDHA	8490	-0.00092	0.25	NO
18	SUCLG2	SUCLG2	SUCLG2	8875	-0.0048	0.23	NO
19	IDH1	IDH1	IDH1	8911	-0.0051	0.23	NO
20	IDH3G	IDH3G	IDH3G	9075	-0.0067	0.23	NO
21	MDH1	MDH1	MDH1	9231	-0.0084	0.22	NO
22	ACO1	ACO1	ACO1	9919	-0.017	0.2	NO
23	IDH2	IDH2	IDH2	10181	-0.02	0.2	NO
24	IDH3B	IDH3B	IDH3B	10351	-0.022	0.21	NO
25	SUCLA2	SUCLA2	SUCLA2	10706	-0.027	0.21	NO
26	DLST	DLST	DLST	10905	-0.03	0.22	NO
27	IDH3A	IDH3A	IDH3A	11580	-0.04	0.21	NO
28	PCK1	PCK1	PCK1	14244	-0.11	0.14	NO
29	PC	PC	PC	14481	-0.12	0.21	NO

Figure S47. Get High-res Image This plot shows mRNAseq_cNMF expression data heatmap (on the left) a RunningEnrichmentScore(RES) plot (on the top right) and a Signal2Noise(S2N) plot (on the bottom right) of genes in the pathway: BIOCARTA TNFR1 PATHWAY.

Figure S48. Get High-res Image For the top 5 core enriched genes in the pathway: BIOCARTA TNFR1 PATHWAY, this volcano plot shows how much they are up/down-regulated and significant. The significance was calculated by empirical bayesian fit

genes ES table in pathway: KEGG CITRATE CYCLE TCA CYCLE

Table S25. Get Full Table This table shows a Running Enrichment Score (RES) of each gene in this pathway, that is, the enrichment score at this point in the ranked list of genes. All genes are ranked by Signal-to-Noise (S2N), a measure of similarity as default and are used to obtain ES matrix of all genes. In this way, GSEA tool uses expression pattern of not only overlapped genes but also not-overlapped genes to produce ES matrix.

Rank	GENE	SYMBOL	DESC	LIST.LOC	S2N	RES	CORE_ENRICHMENT
1	CBLC	CBLC	CBLC	517	0.22	0.0075	YES
2	CDC20	CDC20	CDC20	527	0.22	0.043	YES
3	UBE2C	UBE2C	UBE2C	563	0.21	0.075	YES
4	UBE2E3	UBE2E3	UBE2E3	731	0.18	0.096	YES
5	SKP2	SKP2	SKP2	896	0.16	0.11	YES
6	NHLRC1	NHLRC1	NHLRC1	936	0.16	0.14	YES
7	UBE2NL	UBE2NL	UBE2NL	972	0.15	0.16	YES
8	ANAPC1	ANAPC1	ANAPC1	1486	0.11	0.15	YES
9	CUL7	CUL7	CUL7	2070	0.089	0.13	YES
10	MID1	MID1	MID1	2236	0.083	0.14	YES
11	WWP2	WWP2	WWP2	2368	0.078	0.14	YES
12	TRIM37	TRIM37	TRIM37	2587	0.072	0.14	YES
13	ERCC8	ERCC8	ERCC8	2630	0.072	0.15	YES
14	UBE2I	UBE2I	UBE2I	2756	0.069	0.16	YES
15	PIAS3	PIAS3	PIAS3	2774	0.068	0.17	YES
16	CUL4B	CUL4B	CUL4B	2806	0.068	0.18	YES
17	BRCA1	BRCA1	BRCA1	2865	0.067	0.19	YES
18	CBLB	CBLB	CBLB	2880	0.066	0.2	YES
19	TRIM32	TRIM32	TRIM32	2890	0.066	0.21	YES
20	VHL	VHL	VHL	3251	0.059	0.2	YES
21	SIAH1	SIAH1	SIAH1	3436	0.056	0.2	YES
22	ITCH	ITCH	ITCH	3504	0.054	0.2	YES
23	XIAP	XIAP	XIAP	3520	0.054	0.21	YES
24	RCHY1	RCHY1	RCHY1	3564	0.053	0.22	YES
25	UBE3C	UBE3C	UBE3C	3616	0.052	0.22	YES
26	UBA2	UBA2	UBA2	3646	0.052	0.23	YES
27	RFWD2	RFWD2	RFWD2	3731	0.05	0.23	YES
28	HERC2	HERC2	HERC2	3733	0.05	0.24	YES
29	UBR5	UBR5	UBR5	3907	0.048	0.24	YES
30	UBA3	UBA3	UBA3	3926	0.048	0.25	YES
31	UBE2K	UBE2K	UBE2K	4066	0.046	0.25	YES
32	UBE2G1	UBE2G1	UBE2G1	4307	0.043	0.24	YES
33	CDC26	CDC26	CDC26	4415	0.041	0.24	YES
34	UBE2W	UBE2W	UBE2W	4519	0.04	0.24	YES
35	UBE2Q1	UBE2Q1	UBE2Q1	4554	0.04	0.25	YES
36	HERC1	HERC1	HERC1	4565	0.04	0.25	YES
37	BIRC2	BIRC2	BIRC2	4715	0.038	0.25	YES
38	UBE2J1	UBE2J1	UBE2J1	4893	0.036	0.25	YES
39	BIRC6	BIRC6	BIRC6	4957	0.035	0.25	YES
40	UBE3A	UBE3A	UBE3A	4993	0.034	0.25	YES
41	UBE2J2	UBE2J2	UBE2J2	5024	0.034	0.26	YES
42	UBE2H	UBE2H	UBE2H	5063	0.034	0.26	YES
43	KEAP1	KEAP1	KEAP1	5136	0.033	0.26	YES
44	HUWE1	HUWE1	HUWE1	5242	0.032	0.26	YES
45	UBE2R2	UBE2R2	UBE2R2	5297	0.031	0.26	YES
46	FBXO4	FBXO4	FBXO4	5360	0.03	0.26	YES
47	CUL5	CUL5	CUL5	5388	0.03	0.27	YES
48	PIAS4	PIAS4	PIAS4	5433	0.03	0.27	YES
49	UBE2N	UBE2N	UBE2N	5533	0.028	0.27	YES
50	UBE2Z	UBE2Z	UBE2Z	5621	0.028	0.27	YES
51	FANCL	FANCL	FANCL	5719	0.026	0.27	YES
52	UBE2S	UBE2S	UBE2S	5736	0.026	0.27	YES
53	KLHL9	KLHL9	KLHL9	5760	0.026	0.28	YES
54	HERC4	HERC4	HERC4	5851	0.025	0.27	YES
55	MGRN1	MGRN1	MGRN1	5901	0.025	0.28	YES
56	UBE2O	UBE2O	UBE2O	5951	0.024	0.28	YES
57	FBXW8	FBXW8	FBXW8	6101	0.022	0.27	YES
58	FBXW11	FBXW11	FBXW11	6177	0.022	0.27	YES
59	TRIP12	TRIP12	TRIP12	6194	0.022	0.28	YES
60	TCEB1	TCEB1	TCEB1	6253	0.021	0.28	YES
61	DDB1	DDB1	DDB1	6275	0.021	0.28	YES
62	SYVN1	SYVN1	SYVN1	6316	0.02	0.28	YES
63	ANAPC10	ANAPC10	ANAPC10	6362	0.02	0.28	YES
64	UBE2A	UBE2A	UBE2A	6434	0.019	0.28	NO
65	PIAS2	PIAS2	PIAS2	6522	0.018	0.28	NO
66	UBE2E1	UBE2E1	UBE2E1	6843	0.015	0.26	NO
67	UBE2D2	UBE2D2	UBE2D2	6876	0.015	0.26	NO
68	UBE2Q2	UBE2Q2	UBE2Q2	7044	0.013	0.26	NO
69	UBA6	UBA6	UBA6	7102	0.013	0.25	NO
70	UBE2D3	UBE2D3	UBE2D3	7208	0.012	0.25	NO
71	UBE4B	UBE4B	UBE4B	7322	0.011	0.25	NO
72	CUL2	CUL2	CUL2	7509	0.0088	0.24	NO
73	PRPF19	PRPF19	PRPF19	7672	0.0074	0.23	NO
74	CUL3	CUL3	CUL3	7731	0.0066	0.23	NO
75	CDC16	CDC16	CDC16	7783	0.0062	0.23	NO
76	CDC27	CDC27	CDC27	7831	0.0057	0.22	NO
77	DET1	DET1	DET1	7934	0.0048	0.22	NO
78	NEDD4L	NEDD4L	NEDD4L	8027	0.0038	0.22	NO
79	SKP1	SKP1	SKP1	8033	0.0038	0.22	NO
80	UBE2E2	UBE2E2	UBE2E2	8079	0.0034	0.21	NO
81	WWP1	WWP1	WWP1	8121	0.0029	0.21	NO
82	ANAPC7	ANAPC7	ANAPC7	8235	0.0018	0.2	NO
83	HERC3	HERC3	HERC3	8284	0.0013	0.2	NO
84	ANAPC5	ANAPC5	ANAPC5	8339	0.00064	0.2	NO
85	MAP3K1	MAP3K1	MAP3K1	8381	0.00016	0.2	NO
86	BIRC3	BIRC3	BIRC3	8669	-0.0027	0.18	NO
87	CUL4A	CUL4A	CUL4A	8736	-0.0034	0.18	NO
88	UBE4A	UBE4A	UBE4A	8807	-0.0042	0.18	NO
89	MDM2	MDM2	MDM2	9084	-0.0068	0.16	NO
90	PARK2	PARK2	PARK2	9107	-0.0071	0.16	NO
91	UBA1	UBA1	UBA1	9118	-0.0071	0.16	NO
92	TRAF6	TRAF6	TRAF6	9189	-0.0079	0.16	NO
93	ANAPC2	ANAPC2	ANAPC2	9235	-0.0084	0.16	NO
94	UBE2D1	UBE2D1	UBE2D1	9468	-0.011	0.15	NO
95	UBE2M	UBE2M	UBE2M	9486	-0.012	0.15	NO
96	RBX1	RBX1	RBX1	9500	-0.012	0.15	NO
97	UBE2B	UBE2B	UBE2B	9502	-0.012	0.15	NO
98	RNF7	RNF7	RNF7	9580	-0.012	0.15	NO
99	PML	PML	PML	9672	-0.014	0.15	NO
100	SMURF2	SMURF2	SMURF2	9928	-0.017	0.14	NO
101	FBXW7	FBXW7	FBXW7	9933	-0.017	0.14	NO
102	PPIL2	PPIL2	PPIL2	10055	-0.018	0.14	NO
103	UBE3B	UBE3B	UBE3B	10113	-0.019	0.14	NO
104	CUL1	CUL1	CUL1	10282	-0.021	0.13	NO
105	STUB1	STUB1	STUB1	10350	-0.022	0.13	NO
106	ANAPC11	ANAPC11	ANAPC11	10395	-0.023	0.13	NO
107	PIAS1	PIAS1	PIAS1	10518	-0.024	0.13	NO
108	ANAPC4	ANAPC4	ANAPC4	10571	-0.025	0.13	NO
109	AIRE	AIRE	AIRE	10577	-0.025	0.13	NO
110	UBOX5	UBOX5	UBOX5	10589	-0.026	0.14	NO
111	UBE2F	UBE2F	UBE2F	10612	-0.026	0.14	NO
112	FZR1	FZR1	FZR1	10614	-0.026	0.14	NO
113	TCEB2	TCEB2	TCEB2	10693	-0.027	0.14	NO
114	UBE2L3	UBE2L3	UBE2L3	11042	-0.032	0.13	NO
115	CBL	CBL	CBL	11158	-0.033	0.13	NO
116	SAE1	SAE1	SAE1	11237	-0.034	0.13	NO
117	UBE2L6	UBE2L6	UBE2L6	11240	-0.035	0.14	NO
118	UBE2G2	UBE2G2	UBE2G2	11310	-0.036	0.14	NO
119	CDC23	CDC23	CDC23	11368	-0.037	0.14	NO
120	CDC34	CDC34	CDC34	11758	-0.043	0.13	NO
121	ANAPC13	ANAPC13	ANAPC13	11987	-0.047	0.12	NO
122	UBE2D4	UBE2D4	UBE2D4	12053	-0.049	0.13	NO
123	SMURF1	SMURF1	SMURF1	13193	-0.075	0.076	NO
124	FBXO2	FBXO2	FBXO2	13889	-0.094	0.054	NO
125	RHOBTB2	RHOBTB2	RHOBTB2	14320	-0.11	0.048	NO
126	DDB2	DDB2	DDB2	14617	-0.12	0.052	NO
127	UBE2QL1	UBE2QL1	UBE2QL1	14689	-0.12	0.068	NO
128	NEDD4	NEDD4	NEDD4	14711	-0.12	0.087	NO
129	SOCS1	SOCS1	SOCS1	15061	-0.14	0.091	NO
130	UBA7	UBA7	UBA7	15242	-0.14	0.1	NO
131	KLHL13	KLHL13	KLHL13	16091	-0.18	0.088	NO
132	SOCS3	SOCS3	SOCS3	16198	-0.19	0.11	NO

Figure S49. Get High-res Image This plot shows mRNAseq_cNMF expression data heatmap (on the left) a RunningEnrichmentScore(RES) plot (on the top right) and a Signal2Noise(S2N) plot (on the bottom right) of genes in the pathway: KEGG CITRATE CYCLE TCA CYCLE.

Figure S50. Get High-res Image For the top 5 core enriched genes in the pathway: KEGG CITRATE CYCLE TCA CYCLE, this volcano plot shows how much they are up/down-regulated and significant. The significance was calculated by empirical bayesian fit

genes ES table in pathway: KEGG PENTOSE PHOSPHATE PATHWAY

Table S26. Get Full Table This table shows a Running Enrichment Score (RES) of each gene in this pathway, that is, the enrichment score at this point in the ranked list of genes. All genes are ranked by Signal-to-Noise (S2N), a measure of similarity as default and are used to obtain ES matrix of all genes. In this way, GSEA tool uses expression pattern of not only overlapped genes but also not-overlapped genes to produce ES matrix.

Rank	GENE	SYMBOL	DESC	LIST.LOC	S2N	RES	CORE_ENRICHMENT
1	SNRNP40	SNRNP40	SNRNP40	1228	0.13	-0.03	YES
2	CDC40	CDC40	CDC40	2109	0.087	-0.054	YES
3	SNRPB2	SNRPB2	SNRPB2	2580	0.073	-0.06	YES
4	THOC2	THOC2	THOC2	2598	0.072	-0.04	YES
5	AQR	AQR	AQR	2856	0.067	-0.036	YES
6	PRPF3	PRPF3	PRPF3	3417	0.056	-0.051	YES
7	SNRPA1	SNRPA1	SNRPA1	3551	0.054	-0.043	YES
8	DHX15	DHX15	DHX15	3571	0.053	-0.029	YES
9	PRPF40A	PRPF40A	PRPF40A	3610	0.053	-0.016	YES
10	RBMX	RBMX	RBMX	3626	0.052	-0.0022	YES
11	THOC3	THOC3	THOC3	3659	0.052	0.011	YES
12	SNRPE	SNRPE	SNRPE	3696	0.051	0.023	YES
13	TRA2A	TRA2A	TRA2A	3729	0.051	0.036	YES
14	SNRPF	SNRPF	SNRPF	3837	0.049	0.044	YES
15	SFRS1	SFRS1	SFRS1	4105	0.045	0.042	YES
16	SNRPD3	SNRPD3	SNRPD3	4121	0.045	0.054	YES
17	SNRPG	SNRPG	SNRPG	4156	0.045	0.064	YES
18	PRPF38A	PRPF38A	PRPF38A	4196	0.044	0.075	YES
19	HSPA8	HSPA8	HSPA8	4349	0.042	0.078	YES
20	NCBP1	NCBP1	NCBP1	4363	0.042	0.089	YES
21	SF3B3	SF3B3	SF3B3	4556	0.04	0.09	YES
22	SNRNP200	SNRNP200	SNRNP200	4585	0.039	0.1	YES
23	SFRS6	SFRS6	SFRS6	4592	0.039	0.11	YES
24	HNRNPA1L2	HNRNPA1L2	HNRNPA1L2	4635	0.039	0.12	YES
25	U2AF2	U2AF2	U2AF2	4662	0.038	0.13	YES
26	THOC4	THOC4	THOC4	4675	0.038	0.14	YES
27	DDX46	DDX46	DDX46	4732	0.038	0.15	YES
28	HNRNPK	HNRNPK	HNRNPK	4740	0.038	0.16	YES
29	RBM8A	RBM8A	RBM8A	4841	0.036	0.16	YES
30	SF3B14	SF3B14	SF3B14	4931	0.035	0.17	YES
31	ISY1	ISY1	ISY1	4932	0.035	0.18	YES
32	SF3B1	SF3B1	SF3B1	4966	0.035	0.18	YES
33	HNRNPC	HNRNPC	HNRNPC	4992	0.034	0.19	YES
34	SFRS2	SFRS2	SFRS2	5070	0.034	0.2	YES
35	SFRS13A	SFRS13A	SFRS13A	5126	0.033	0.2	YES
36	HNRNPU	HNRNPU	HNRNPU	5143	0.033	0.21	YES
37	SNRPD1	SNRPD1	SNRPD1	5294	0.031	0.21	YES
38	CDC5L	CDC5L	CDC5L	5394	0.03	0.22	YES
39	SFRS9	SFRS9	SFRS9	5416	0.03	0.22	YES
40	SMNDC1	SMNDC1	SMNDC1	5452	0.029	0.23	YES
41	PRPF4	PRPF4	PRPF4	5472	0.029	0.24	YES
42	SNRPB	SNRPB	SNRPB	5493	0.029	0.24	YES
43	LSM2	LSM2	LSM2	5504	0.029	0.25	YES
44	SF3A2	SF3A2	SF3A2	5557	0.028	0.26	YES
45	CHERP	CHERP	CHERP	5573	0.028	0.26	YES
46	PPIH	PPIH	PPIH	5616	0.028	0.27	YES
47	SNRNP27	SNRNP27	SNRNP27	5632	0.027	0.28	YES
48	DDX42	DDX42	DDX42	5633	0.027	0.28	YES
49	SLU7	SLU7	SLU7	5666	0.027	0.29	YES
50	HNRNPA1	HNRNPA1	HNRNPA1	5676	0.027	0.3	YES
51	RBM22	RBM22	RBM22	5825	0.025	0.3	YES
52	THOC1	THOC1	THOC1	5839	0.025	0.3	YES
53	TCERG1	TCERG1	TCERG1	5943	0.024	0.3	YES
54	SYF2	SYF2	SYF2	6003	0.023	0.31	YES
55	BCAS2	BCAS2	BCAS2	6028	0.023	0.31	YES
56	NAA38	NAA38	NAA38	6100	0.023	0.31	YES
57	MAGOH	MAGOH	MAGOH	6104	0.022	0.32	YES
58	PRPF8	PRPF8	PRPF8	6326	0.02	0.31	YES
59	SF3B4	SF3B4	SF3B4	6352	0.02	0.32	YES
60	PRPF6	PRPF6	PRPF6	6366	0.02	0.32	YES
61	U2AF1	U2AF1	U2AF1	6438	0.019	0.32	YES
62	SNRPD2	SNRPD2	SNRPD2	6569	0.018	0.32	YES
63	EIF4A3	EIF4A3	EIF4A3	6683	0.017	0.32	YES
64	RBM17	RBM17	RBM17	6728	0.016	0.32	YES
65	PRPF38B	PRPF38B	PRPF38B	6752	0.016	0.33	YES
66	PLRG1	PLRG1	PLRG1	6789	0.016	0.33	YES
67	RBM25	RBM25	RBM25	6796	0.016	0.33	YES
68	PQBP1	PQBP1	PQBP1	6866	0.015	0.33	YES
69	SF3A3	SF3A3	SF3A3	6886	0.015	0.34	YES
70	BAT1	BAT1	BAT1	6895	0.015	0.34	YES
71	PCBP1	PCBP1	PCBP1	6910	0.015	0.34	YES
72	SNRNP70	SNRNP70	SNRNP70	6916	0.014	0.35	YES
73	SNW1	SNW1	SNW1	6946	0.014	0.35	YES
74	SNRPC	SNRPC	SNRPC	6963	0.014	0.35	YES
75	SFRS3	SFRS3	SFRS3	7008	0.014	0.36	YES
76	PUF60	PUF60	PUF60	7091	0.013	0.35	YES
77	CWC15	CWC15	CWC15	7182	0.012	0.35	YES
78	SF3B2	SF3B2	SF3B2	7225	0.012	0.35	YES
79	USP39	USP39	USP39	7251	0.011	0.36	YES
80	DDX23	DDX23	DDX23	7258	0.011	0.36	YES
81	PHF5A	PHF5A	PHF5A	7289	0.011	0.36	YES
82	SF3A1	SF3A1	SF3A1	7308	0.011	0.36	YES
83	SR140	SR140	SR140	7348	0.01	0.36	YES
84	DDX5	DDX5	DDX5	7416	0.0097	0.36	YES
85	CRNKL1	CRNKL1	CRNKL1	7447	0.0094	0.36	YES
86	PRPF19	PRPF19	PRPF19	7672	0.0074	0.35	NO
87	HNRNPA3	HNRNPA3	HNRNPA3	7759	0.0064	0.35	NO
88	DHX8	DHX8	DHX8	7816	0.0058	0.35	NO
89	HNRNPM	HNRNPM	HNRNPM	8015	0.0039	0.34	NO
90	SFRS7	SFRS7	SFRS7	8073	0.0034	0.34	NO
91	LSM7	LSM7	LSM7	8081	0.0033	0.34	NO
92	ACIN1	ACIN1	ACIN1	8196	0.0023	0.33	NO
93	EFTUD2	EFTUD2	EFTUD2	8220	0.002	0.33	NO
94	PRPF18	PRPF18	PRPF18	8279	0.0014	0.33	NO
95	LSM4	LSM4	LSM4	8387	0.0001	0.32	NO
96	TRA2B	TRA2B	TRA2B	8493	-0.00095	0.32	NO
97	SNRPA	SNRPA	SNRPA	8624	-0.0022	0.31	NO
98	SFRS5	SFRS5	SFRS5	8723	-0.0032	0.3	NO
99	DHX16	DHX16	DHX16	8752	-0.0035	0.3	NO
100	LSM5	LSM5	LSM5	8854	-0.0045	0.3	NO
101	MAGOHB	MAGOHB	MAGOHB	8910	-0.0051	0.3	NO
102	WBP11	WBP11	WBP11	8944	-0.0054	0.3	NO
103	LSM3	LSM3	LSM3	8965	-0.0057	0.3	NO
104	PRPF31	PRPF31	PRPF31	8977	-0.0058	0.3	NO
105	XAB2	XAB2	XAB2	8980	-0.0058	0.3	NO
106	PPIE	PPIE	PPIE	9021	-0.0062	0.3	NO
107	SFRS4	SFRS4	SFRS4	9149	-0.0075	0.3	NO
108	SFRS2B	SFRS2B	SFRS2B	9185	-0.0079	0.3	NO
109	PPIL1	PPIL1	PPIL1	9295	-0.0093	0.29	NO
110	CTNNBL1	CTNNBL1	CTNNBL1	9432	-0.011	0.29	NO
111	TXNL4A	TXNL4A	TXNL4A	9636	-0.013	0.28	NO
112	LSM6	LSM6	LSM6	9721	-0.014	0.28	NO
113	PRPF40B	PRPF40B	PRPF40B	9806	-0.015	0.28	NO
114	SART1	SART1	SART1	9924	-0.017	0.28	NO
115	ZMAT2	ZMAT2	ZMAT2	9957	-0.017	0.28	NO
116	NHP2L1	NHP2L1	NHP2L1	10180	-0.02	0.27	NO
117	BUD31	BUD31	BUD31	10267	-0.021	0.28	NO
118	DHX38	DHX38	DHX38	10285	-0.022	0.28	NO
119	HSPA6	HSPA6	HSPA6	10348	-0.022	0.28	NO
120	HSPA1L	HSPA1L	HSPA1L	10635	-0.026	0.28	NO
121	CCDC12	CCDC12	CCDC12	11000	-0.031	0.26	NO
122	HSPA1B	HSPA1B	HSPA1B	11415	-0.037	0.25	NO
123	SF3B5	SF3B5	SF3B5	11618	-0.041	0.25	NO
124	HSPA1A	HSPA1A	HSPA1A	12864	-0.067	0.2	NO
125	HSPA2	HSPA2	HSPA2	17779	-0.34	0.026	NO

Figure S51. Get High-res Image This plot shows mRNAseq_cNMF expression data heatmap (on the left) a RunningEnrichmentScore(RES) plot (on the top right) and a Signal2Noise(S2N) plot (on the bottom right) of genes in the pathway: KEGG PENTOSE PHOSPHATE PATHWAY.

Figure S52. Get High-res Image For the top 5 core enriched genes in the pathway: KEGG PENTOSE PHOSPHATE PATHWAY, this volcano plot shows how much they are up/down-regulated and significant. The significance was calculated by empirical bayesian fit

genes ES table in pathway: KEGG N GLYCAN BIOSYNTHESIS

Table S27. Get Full Table This table shows a Running Enrichment Score (RES) of each gene in this pathway, that is, the enrichment score at this point in the ranked list of genes. All genes are ranked by Signal-to-Noise (S2N), a measure of similarity as default and are used to obtain ES matrix of all genes. In this way, GSEA tool uses expression pattern of not only overlapped genes but also not-overlapped genes to produce ES matrix.

Rank	GENE	SYMBOL	DESC	LIST.LOC	S2N	RES	CORE_ENRICHMENT
1	CDC45	CDC45	CDC45	354	0.26	0.0083	YES
2	BUB1B	BUB1B	BUB1B	355	0.26	0.036	YES
3	CCNE2	CCNE2	CCNE2	374	0.26	0.062	YES
4	CDKN2A	CDKN2A	CDKN2A	406	0.24	0.086	YES
5	TTK	TTK	TTK	453	0.23	0.11	YES
6	CDC20	CDC20	CDC20	527	0.22	0.13	YES
7	SMC1B	SMC1B	SMC1B	571	0.21	0.15	YES
8	CCNB2	CCNB2	CCNB2	621	0.2	0.16	YES
9	BUB1	BUB1	BUB1	653	0.2	0.18	YES
10	ESPL1	ESPL1	ESPL1	764	0.18	0.2	YES
11	CDC25C	CDC25C	CDC25C	783	0.18	0.21	YES
12	PLK1	PLK1	PLK1	853	0.17	0.23	YES
13	CCNA2	CCNA2	CCNA2	856	0.17	0.24	YES
14	SKP2	SKP2	SKP2	896	0.16	0.26	YES
15	E2F3	E2F3	E2F3	1047	0.15	0.27	YES
16	ORC1L	ORC1L	ORC1L	1062	0.15	0.28	YES
17	HDAC1	HDAC1	HDAC1	1276	0.13	0.28	YES
18	CDK1	CDK1	CDK1	1344	0.12	0.29	YES
19	ANAPC1	ANAPC1	ANAPC1	1486	0.11	0.3	YES
20	E2F2	E2F2	E2F2	1535	0.11	0.31	YES
21	HDAC2	HDAC2	HDAC2	1552	0.11	0.32	YES
22	MAD2L1	MAD2L1	MAD2L1	1606	0.11	0.33	YES
23	CCNB1	CCNB1	CCNB1	1610	0.11	0.34	YES
24	E2F5	E2F5	E2F5	1733	0.1	0.34	YES
25	ORC6L	ORC6L	ORC6L	1791	0.099	0.35	YES
26	ATR	ATR	ATR	1908	0.095	0.35	YES
27	ORC3L	ORC3L	ORC3L	2097	0.088	0.35	YES
28	GSK3B	GSK3B	GSK3B	2217	0.084	0.35	YES
29	PKMYT1	PKMYT1	PKMYT1	2226	0.083	0.36	YES
30	TFDP1	TFDP1	TFDP1	2258	0.082	0.37	YES
31	MCM2	MCM2	MCM2	2315	0.08	0.37	YES
32	PTTG1	PTTG1	PTTG1	2342	0.079	0.38	YES
33	WEE1	WEE1	WEE1	2451	0.076	0.38	YES
34	CDK7	CDK7	CDK7	2968	0.064	0.36	YES
35	STAG2	STAG2	STAG2	2975	0.064	0.37	YES
36	CDC6	CDC6	CDC6	3225	0.059	0.36	YES
37	MYC	MYC	MYC	3228	0.059	0.37	YES
38	ORC2L	ORC2L	ORC2L	3229	0.059	0.37	YES
39	ORC4L	ORC4L	ORC4L	3313	0.058	0.37	YES
40	MCM4	MCM4	MCM4	3347	0.057	0.38	YES
41	PRKDC	PRKDC	PRKDC	3350	0.057	0.38	YES
42	CDK4	CDK4	CDK4	3438	0.056	0.39	YES
43	CHEK2	CHEK2	CHEK2	3456	0.055	0.39	YES
44	MCM6	MCM6	MCM6	3490	0.055	0.39	YES
45	SMC3	SMC3	SMC3	3636	0.052	0.39	YES
46	RAD21	RAD21	RAD21	3685	0.051	0.4	YES
47	BUB3	BUB3	BUB3	3737	0.05	0.4	YES
48	ATM	ATM	ATM	3900	0.048	0.39	NO
49	CDC26	CDC26	CDC26	4415	0.041	0.37	NO
50	CDC7	CDC7	CDC7	4689	0.038	0.36	NO
51	E2F1	E2F1	E2F1	4748	0.038	0.36	NO
52	SMAD2	SMAD2	SMAD2	4771	0.037	0.36	NO
53	EP300	EP300	EP300	5042	0.034	0.35	NO
54	YWHAQ	YWHAQ	YWHAQ	5280	0.031	0.34	NO
55	CDC14A	CDC14A	CDC14A	5332	0.031	0.34	NO
56	RBL1	RBL1	RBL1	5395	0.03	0.34	NO
57	MCM7	MCM7	MCM7	5428	0.03	0.34	NO
58	PCNA	PCNA	PCNA	5807	0.026	0.32	NO
59	YWHAZ	YWHAZ	YWHAZ	5905	0.025	0.32	NO
60	ANAPC10	ANAPC10	ANAPC10	6362	0.02	0.3	NO
61	RB1	RB1	RB1	6369	0.02	0.3	NO
62	YWHAB	YWHAB	YWHAB	6402	0.019	0.3	NO
63	ABL1	ABL1	ABL1	6484	0.019	0.3	NO
64	CCNB3	CCNB3	CCNB3	6507	0.018	0.3	NO
65	CREBBP	CREBBP	CREBBP	6523	0.018	0.3	NO
66	YWHAE	YWHAE	YWHAE	6553	0.018	0.3	NO
67	STAG1	STAG1	STAG1	6769	0.016	0.29	NO
68	SMC1A	SMC1A	SMC1A	7023	0.013	0.28	NO
69	YWHAG	YWHAG	YWHAG	7065	0.013	0.28	NO
70	ORC5L	ORC5L	ORC5L	7188	0.012	0.27	NO
71	MCM3	MCM3	MCM3	7227	0.012	0.27	NO
72	CDK2	CDK2	CDK2	7428	0.0096	0.26	NO
73	CDC16	CDC16	CDC16	7783	0.0062	0.24	NO
74	CDC27	CDC27	CDC27	7831	0.0057	0.24	NO
75	CCNH	CCNH	CCNH	7937	0.0048	0.23	NO
76	SKP1	SKP1	SKP1	8033	0.0038	0.23	NO
77	CHEK1	CHEK1	CHEK1	8074	0.0034	0.23	NO
78	ANAPC7	ANAPC7	ANAPC7	8235	0.0018	0.22	NO
79	CDKN1B	CDKN1B	CDKN1B	8258	0.0016	0.22	NO
80	ANAPC5	ANAPC5	ANAPC5	8339	0.00064	0.21	NO
81	ZBTB17	ZBTB17	ZBTB17	8651	-0.0026	0.2	NO
82	E2F4	E2F4	E2F4	8747	-0.0034	0.19	NO
83	RBL2	RBL2	RBL2	8837	-0.0044	0.19	NO
84	MDM2	MDM2	MDM2	9084	-0.0068	0.17	NO
85	TP53	TP53	TP53	9093	-0.0069	0.18	NO
86	MCM5	MCM5	MCM5	9170	-0.0078	0.17	NO
87	ANAPC2	ANAPC2	ANAPC2	9235	-0.0084	0.17	NO
88	TFDP2	TFDP2	TFDP2	9458	-0.011	0.16	NO
89	WEE2	WEE2	WEE2	9463	-0.011	0.16	NO
90	RBX1	RBX1	RBX1	9500	-0.012	0.16	NO
91	MAD2L2	MAD2L2	MAD2L2	9551	-0.012	0.16	NO
92	CCND3	CCND3	CCND3	9670	-0.014	0.15	NO
93	CUL1	CUL1	CUL1	10282	-0.021	0.12	NO
94	ANAPC11	ANAPC11	ANAPC11	10395	-0.023	0.12	NO
95	ANAPC4	ANAPC4	ANAPC4	10571	-0.025	0.11	NO
96	FZR1	FZR1	FZR1	10614	-0.026	0.11	NO
97	CDKN2B	CDKN2B	CDKN2B	10794	-0.028	0.1	NO
98	CCNE1	CCNE1	CCNE1	10886	-0.029	0.1	NO
99	SMAD3	SMAD3	SMAD3	11051	-0.032	0.095	NO
100	TGFB1	TGFB1	TGFB1	11196	-0.034	0.091	NO
101	CDC23	CDC23	CDC23	11368	-0.037	0.085	NO
102	SMAD4	SMAD4	SMAD4	11397	-0.037	0.088	NO
103	CDC25B	CDC25B	CDC25B	11613	-0.04	0.08	NO
104	YWHAH	YWHAH	YWHAH	11867	-0.045	0.071	NO
105	ANAPC13	ANAPC13	ANAPC13	11987	-0.047	0.069	NO
106	PTTG2	PTTG2	PTTG2	12459	-0.057	0.049	NO
107	CCND1	CCND1	CCND1	12651	-0.062	0.045	NO
108	SFN	SFN	SFN	13070	-0.072	0.03	NO
109	GADD45A	GADD45A	GADD45A	13553	-0.084	0.012	NO
110	CDC25A	CDC25A	CDC25A	13570	-0.085	0.02	NO
111	GADD45G	GADD45G	GADD45G	13960	-0.097	0.0089	NO
112	MAD1L1	MAD1L1	MAD1L1	14040	-0.099	0.015	NO
113	TGFB2	TGFB2	TGFB2	14184	-0.1	0.018	NO
114	CCNA1	CCNA1	CCNA1	14928	-0.13	-0.0088	NO
115	CDKN2D	CDKN2D	CDKN2D	15153	-0.14	-0.0063	NO
116	CCND2	CCND2	CCND2	15429	-0.15	-0.0054	NO
117	CDC14B	CDC14B	CDC14B	15556	-0.16	0.0043	NO
118	GADD45B	GADD45B	GADD45B	15777	-0.17	0.0099	NO
119	CDKN1C	CDKN1C	CDKN1C	16092	-0.18	0.012	NO
120	CDKN2C	CDKN2C	CDKN2C	16217	-0.19	0.025	NO
121	CDKN1A	CDKN1A	CDKN1A	16223	-0.19	0.045	NO
122	CDK6	CDK6	CDK6	17609	-0.31	0.0014	NO
123	TGFB3	TGFB3	TGFB3	17709	-0.32	0.03	NO

Figure S53. Get High-res Image This plot shows mRNAseq_cNMF expression data heatmap (on the left) a RunningEnrichmentScore(RES) plot (on the top right) and a Signal2Noise(S2N) plot (on the bottom right) of genes in the pathway: KEGG N GLYCAN BIOSYNTHESIS.

Figure S54. Get High-res Image For the top 5 core enriched genes in the pathway: KEGG N GLYCAN BIOSYNTHESIS, this volcano plot shows how much they are up/down-regulated and significant. The significance was calculated by empirical bayesian fit

genes ES table in pathway: KEGG AMINOACYL TRNA BIOSYNTHESIS

Table S28. Get Full Table This table shows a Running Enrichment Score (RES) of each gene in this pathway, that is, the enrichment score at this point in the ranked list of genes. All genes are ranked by Signal-to-Noise (S2N), a measure of similarity as default and are used to obtain ES matrix of all genes. In this way, GSEA tool uses expression pattern of not only overlapped genes but also not-overlapped genes to produce ES matrix.

Rank	GENE	SYMBOL	DESC	LIST.LOC	S2N	RES	CORE_ENRICHMENT
1	TAF4B	TAF4B	TAF4B	1036	0.15	0.028	YES
2	TAF1L	TAF1L	TAF1L	1350	0.12	0.082	YES
3	GTF2H2	GTF2H2	GTF2H2	1645	0.11	0.13	YES
4	TAF2	TAF2	TAF2	2264	0.082	0.14	YES
5	TAF4	TAF4	TAF4	2418	0.077	0.18	YES
6	TAF1	TAF1	TAF1	2428	0.077	0.22	YES
7	GTF2E1	GTF2E1	GTF2E1	2441	0.076	0.26	YES
8	GTF2H3	GTF2H3	GTF2H3	2505	0.074	0.3	YES
9	STON1	STON1	STON1	2707	0.07	0.33	YES
10	GTF2I	GTF2I	GTF2I	3585	0.053	0.31	YES
11	GTF2IRD1	GTF2IRD1	GTF2IRD1	3675	0.051	0.34	YES
12	TAF9	TAF9	TAF9	4325	0.042	0.32	YES
13	GTF2A1L	GTF2A1L	GTF2A1L	4406	0.042	0.34	YES
14	TAF7	TAF7	TAF7	4618	0.039	0.36	YES
15	GTF2A1	GTF2A1	GTF2A1	4652	0.039	0.38	YES
16	TAF5L	TAF5L	TAF5L	5020	0.034	0.38	NO
17	GTF2A2	GTF2A2	GTF2A2	5815	0.026	0.35	NO
18	GTF2H1	GTF2H1	GTF2H1	5835	0.025	0.36	NO
19	TAF9B	TAF9B	TAF9B	5911	0.025	0.37	NO
20	TAF6L	TAF6L	TAF6L	6325	0.02	0.36	NO
21	GTF2E2	GTF2E2	GTF2E2	7326	0.011	0.31	NO
22	TAF11	TAF11	TAF11	7452	0.0093	0.31	NO
23	GTF2H4	GTF2H4	GTF2H4	7900	0.0051	0.29	NO
24	TAF5	TAF5	TAF5	7948	0.0047	0.29	NO
25	TBP	TBP	TBP	8044	0.0037	0.28	NO
26	TAF12	TAF12	TAF12	9030	-0.0063	0.23	NO
27	GTF2F2	GTF2F2	GTF2F2	9147	-0.0074	0.23	NO
28	TAF10	TAF10	TAF10	9234	-0.0084	0.23	NO
29	GTF2F1	GTF2F1	GTF2F1	9714	-0.014	0.21	NO
30	TAF13	TAF13	TAF13	9810	-0.015	0.22	NO
31	TAF6	TAF6	TAF6	9958	-0.017	0.22	NO
32	GTF2B	GTF2B	GTF2B	11880	-0.045	0.14	NO
33	TBPL1	TBPL1	TBPL1	14566	-0.12	0.059	NO
34	TAF7L	TAF7L	TAF7L	17102	-0.25	0.063	NO

Figure S55. Get High-res Image This plot shows mRNAseq_cNMF expression data heatmap (on the left) a RunningEnrichmentScore(RES) plot (on the top right) and a Signal2Noise(S2N) plot (on the bottom right) of genes in the pathway: KEGG AMINOACYL TRNA BIOSYNTHESIS.

Figure S56. Get High-res Image For the top 5 core enriched genes in the pathway: KEGG AMINOACYL TRNA BIOSYNTHESIS, this volcano plot shows how much they are up/down-regulated and significant. The significance was calculated by empirical bayesian fit

genes ES table in pathway: KEGG RIBOSOME

Table S29. Get Full Table This table shows a Running Enrichment Score (RES) of each gene in this pathway, that is, the enrichment score at this point in the ranked list of genes. All genes are ranked by Signal-to-Noise (S2N), a measure of similarity as default and are used to obtain ES matrix of all genes. In this way, GSEA tool uses expression pattern of not only overlapped genes but also not-overlapped genes to produce ES matrix.

Rank	GENE	SYMBOL	DESC	LIST.LOC	S2N	RES	CORE_ENRICHMENT
1	ARHGDIB	ARHGDIB	ARHGDIB	704	0.19	0.064	YES
2	CASP2	CASP2	CASP2	875	0.16	0.14	YES
3	LMNB1	LMNB1	LMNB1	979	0.15	0.22	YES
4	MAPK8	MAPK8	MAPK8	1388	0.12	0.27	YES
5	DFFB	DFFB	DFFB	2233	0.083	0.27	YES
6	PARP1	PARP1	PARP1	2727	0.07	0.28	YES
7	PRKDC	PRKDC	PRKDC	3350	0.057	0.27	YES
8	MAP3K7	MAP3K7	MAP3K7	3383	0.056	0.3	YES
9	CASP8	CASP8	CASP8	3604	0.053	0.32	YES
10	CASP3	CASP3	CASP3	3750	0.05	0.34	YES
11	LMNB2	LMNB2	LMNB2	3889	0.048	0.36	YES
12	MADD	MADD	MADD	6156	0.022	0.25	NO
13	RB1	RB1	RB1	6369	0.02	0.25	NO
14	PAK2	PAK2	PAK2	7430	0.0096	0.19	NO
15	PAK1	PAK1	PAK1	7676	0.0074	0.18	NO
16	SPTAN1	SPTAN1	SPTAN1	8360	0.00042	0.15	NO
17	DFFA	DFFA	DFFA	8378	0.0002	0.14	NO
18	MAP3K1	MAP3K1	MAP3K1	8381	0.00016	0.14	NO
19	BAG4	BAG4	BAG4	10688	-0.027	0.033	NO
20	CRADD	CRADD	CRADD	10861	-0.029	0.04	NO
21	FADD	FADD	FADD	11208	-0.034	0.04	NO
22	RIPK1	RIPK1	RIPK1	11675	-0.041	0.037	NO
23	TRADD	TRADD	TRADD	11862	-0.045	0.052	NO
24	MAP2K4	MAP2K4	MAP2K4	12800	-0.065	0.036	NO
25	TNFRSF1A	TNFRSF1A	TNFRSF1A	13268	-0.077	0.052	NO
26	LMNA	LMNA	LMNA	13935	-0.096	0.068	NO
27	JUN	JUN	JUN	13978	-0.097	0.12	NO
28	TNF	TNF	TNF	16582	-0.21	0.092	NO

Figure S57. Get High-res Image This plot shows mRNAseq_cNMF expression data heatmap (on the left) a RunningEnrichmentScore(RES) plot (on the top right) and a Signal2Noise(S2N) plot (on the bottom right) of genes in the pathway: KEGG RIBOSOME.

Figure S58. Get High-res Image For the top 5 core enriched genes in the pathway: KEGG RIBOSOME, this volcano plot shows how much they are up/down-regulated and significant. The significance was calculated by empirical bayesian fit

genes ES table in pathway: KEGG RNA DEGRADATION

Table S30. Get Full Table This table shows a Running Enrichment Score (RES) of each gene in this pathway, that is, the enrichment score at this point in the ranked list of genes. All genes are ranked by Signal-to-Noise (S2N), a measure of similarity as default and are used to obtain ES matrix of all genes. In this way, GSEA tool uses expression pattern of not only overlapped genes but also not-overlapped genes to produce ES matrix.

Rank	GENE	SYMBOL	DESC	LIST.LOC	S2N	RES	CORE_ENRICHMENT
1	MYT1	MYT1	MYT1	41	0.53	0.22	YES
2	CDC25C	CDC25C	CDC25C	783	0.18	0.25	YES
3	CDK1	CDK1	CDK1	1344	0.12	0.27	YES
4	CCNB1	CCNB1	CCNB1	1610	0.11	0.3	YES
5	PAQR5	PAQR5	PAQR5	2138	0.086	0.31	YES
6	PRKAR1B	PRKAR1B	PRKAR1B	2201	0.084	0.34	YES
7	GNAI1	GNAI1	GNAI1	2949	0.065	0.32	NO
8	ACTR3	ACTR3	ACTR3	4694	0.038	0.24	NO
9	PRKACB	PRKACB	PRKACB	5285	0.031	0.23	NO
10	ARPC3	ARPC3	ARPC3	5317	0.031	0.24	NO
11	GNB1	GNB1	GNB1	5320	0.031	0.25	NO
12	PRKAR2A	PRKAR2A	PRKAR2A	6134	0.022	0.21	NO
13	RPS6KA1	RPS6KA1	RPS6KA1	6411	0.019	0.21	NO
14	ACTR2	ACTR2	ACTR2	6655	0.017	0.2	NO
15	GNAS	GNAS	GNAS	6880	0.015	0.2	NO
16	ARPC5	ARPC5	ARPC5	7057	0.013	0.19	NO
17	PRKAR1A	PRKAR1A	PRKAR1A	7168	0.012	0.19	NO
18	ARPC1B	ARPC1B	ARPC1B	9369	-0.01	0.073	NO
19	ARPC1A	ARPC1A	ARPC1A	9414	-0.011	0.075	NO
20	ARPC2	ARPC2	ARPC2	9443	-0.011	0.078	NO
21	MAPK1	MAPK1	MAPK1	9459	-0.011	0.082	NO
22	SRC	SRC	SRC	9754	-0.015	0.072	NO
23	ARPC4	ARPC4	ARPC4	9992	-0.018	0.066	NO
24	CAP1	CAP1	CAP1	10773	-0.028	0.035	NO
25	PIN1	PIN1	PIN1	11370	-0.037	0.017	NO
26	HRAS	HRAS	HRAS	11878	-0.045	0.0084	NO
27	MAPK3	MAPK3	MAPK3	12256	-0.053	0.0098	NO
28	PAQR7	PAQR7	PAQR7	12476	-0.058	0.022	NO
29	PRKAR2B	PRKAR2B	PRKAR2B	14218	-0.1	-0.03	NO
30	PGR	PGR	PGR	17092	-0.25	-0.084	NO
31	ACTA1	ACTA1	ACTA1	17870	-0.36	0.021	NO

Figure S59. Get High-res Image This plot shows mRNAseq_cNMF expression data heatmap (on the left) a RunningEnrichmentScore(RES) plot (on the top right) and a Signal2Noise(S2N) plot (on the bottom right) of genes in the pathway: KEGG RNA DEGRADATION.

Figure S60. Get High-res Image For the top 5 core enriched genes in the pathway: KEGG RNA DEGRADATION, this volcano plot shows how much they are up/down-regulated and significant. The significance was calculated by empirical bayesian fit

Fold change

For the top enriched genes, if you want to check whether they are

up-regulated, please check the list of up-regulated genes
down-regulated, please check the list of down-regulated genes

Expression level

For the top enriched genes, if you want to check whether they are

highly expressed genes, please check the list of high (top 30%) expressed genes
low expressed genes, please check the list of low (bottom 30%) expressed genes

An expression pattern of top(30%)/middle(30%)/low(30%) in this subtype against other subtypes is available in a heatmap

Significant gene list

For the top enriched genes, if you want to check whether they are

significantly differently expressed genes by eBayes lm fit, please check the list of significant genes

Methods & Data

Input

Gene set database = c2.cp.v3.0-2.symbols.gmt
Expression data file = PRAD-TP.uncv2.mRNAseq_RSEM_normalized_log2.txt
Phenotype data file = PRAD-TP.mergedcluster.txt

GSEA analysis

For the Gene Set Enrichment Analysis (GSEA), Broad GSEA-P-R.1.0 version is used with class2: canonical pathways geneses from MSigDB. Further details about statistics are available inThe Broad GSEA website.

Download Results

In addition to the links below, the full results of the analysis summarized in this report can also be downloaded programmatically using firehose_get, or interactively from either the Broad GDAC website or TCGA Data Coordination Center Portal.

References

[1] Subramanian, A. et al, Gene set enrichment analysis: A knowledge-based approach for interpreting genome-wide expression profiles., Proc. Natl. Acad. Sci. USA 102(43) (2005)

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